IMPACT OF AG NANOPARTICLES ON MICROORGANISMS, CAUSATIVE AGENTS OF PURULENT-INFLAMMATORY PROCESSES.

Determination of Ag nanoparticles impact on microorganisms causative agents of purulent-inflammatory processes was carried out and it was stated that the greatest significance of growth inhibition zone was found in Staphylococcus aureus and Streptococcus pyogenes with sample length from 1 to 6 mm and Escherichia coli with 5-6 mm sample length. The investigated strains in an amount 104 - 106 CFU/ml were sensitive to Аg nanoparticles activity, but at concentration 108 CFU/ml and more all strains were found persistent to samples of various length. The ability to form biofilms with planktonic cells of microorganisms under Ag nanoparticles activity sufficiently reduced from 3.4 (Candida albicans) to 5.5 (Klebsiella pneumonia) in investigated strains. The disorganization of daily biofilms was found in determining of Ag nanoparticles impact on formed biofilms of microorganisms.

Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products.

Enhanced oxidative stress is involved in the progression of renal disease. Since angiotensin converting enzyme inhibitors (ACEI) have been shown to improve the antioxidative defence, we investigated, in patients with nondiabetic nephropathy, the short-term effect of the ACEI ramipril on parameters of oxidative stress, such as advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), homocysteine (Hcy), and lipid peroxidation products. Ramipril (2.5-5.0 mg/day) was administered to 12 newly diagnosed patients for 2 months and data compared with a patient group under conventional therapy (diuretic/beta-blockers) and with age- and sex-matched healthy subjects (CTRL). Patients had mild to moderate renal insufficiency and showed, in the plasma, higher fluorescent AGE and carboxymethyllysine (CML) levels, as well as elevated concentrations of AOPPs, lipofuscin and Hcy when compared with CTRL. Basal data of the patients on conventional therapy did not differ significantly from the ramipril group, except for higher Hcy levels in the latter. Administration of ramipril resulted in a drop in blood pressure and proteinuria, while creatinine clearance remained the same. The fluorescent AGEs exhibited a mild but significant decline, yet CML concentration was unchanged. The AOPP and malondialdehyde concentrations decreased, while a small rise in neopterin levels was evident after treatment. The mentioned parameters were not affected significantly in the conventionally treated patients. Evidence that ramipril administration results in a mild decline of fluorescent AGEs is herein presented for the first time. The underlying mechanism may be decreased oxidative stress, as indicated by a decline in AOPPs and malondialdehyde.

[Changes in serum levels of lipid peroxidation products during labor and in the puerperium]. / Zmeny sérových hladín produktov lipoperoxidácie pocas pôrodu a v sestonedelí.

OBJECTIVE: To determine the activity of reactive oxygen species (ROS) during labour by characterizing changes in maternal serum levels of lipid peroxidation end-products--MDA and lipofuscin during labour and the early post-partum period. We also tried to evaluate the relationship between levels of lipid peroxides and some clinical characteristics of labour. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynaecology LFUK, Bratislava; Department of clinical laboratories, Ministry of defense SR, Bratislava. METHODS: Blood samples were obtained from 66 pregnant women with uncomplicated pregnancy at the end of labour and during the early post-partum period. The control group consisted of 19 pregnant women delivering by primary Cesarean section. Blood samples were examined for MDA and lipofuscin by HPLC method. We used paired and unpaired Student's t-test to statistically evaluate our results. RESULTS: MDA and lipofuscin levels in pregnant women delivering spontaneously compared to those delivering by C-section were significantly elevated (P < 0.05). MDA and lipofuscin levels in pregnant women during spontaneous labour or during by C-section compared to the levels in early post-partum period were not significantly increased. We have not found any correlation between the length of the labour and lipoperoxides concentration.

[Increased levels of circulating advanced glycation end products in a model of acute renal insufficiency in rats]. / Zvýsenie koncentrácií cirkulujúcich koncových produktov pokrocilej glykácie v modeli akútnej renálnej insuficiencie u potkana.

BACKGROUND: Advanced glycation end products (AGEs) are formed from proteins and peptides by non-enzymatic glycation or glycooxidation. AGEs are formed slowly during aging, and they accumulate in circulation and tissues in diabetes and chronic renal failure. Kidney plays a key role in the disposal of AGEs. Aim of this study was to verify the hypothesis that, acute loss of renal function with enhanced oxidative and carbonyl stress should result in a rise of circulating AGEs levels. METHOD AND RESULTS: Acute renal failure (ARI) was induced in rats by bilateral nephrectomy (24-72 hours). The data on AGEs levels, oxidative status and antioxidative defense was compared to those of sham operated animals. 48 hours after the induction of ARI concentrations of AGEs, determined fluorimetrically or as carboxymethyllysine, rose 2-fold, and they correlated with concentrations of creatinine (r = 0.938, p < 0.001 and r = 0.815, p < 0.001, respectively). Malondialdehyde (MDA) and lipofuscine (LF) concentrations rose in a time dependent manner, suggesting an enhanced oxidative and carbonyl stress. Enhanced lipid peroxidation did not result from the suppressed antioxidant defense: activity of superoxide dismutase rose by 50%, while that of glutathione peroxidase was not compromised. Total antioxidant status increased, probably due to the accumulation of uremic toxins with scavenging capacity, such as hyppurate. CONCLUSIONS: According to our knowledge our data was first to show a rapid increase in circulating AGEs concentrations in the model of acute renal failure in rats. If AGEs accumulate in acute renal failure in humans, their contribution to acute toxicity, and/or to the development of later complications, might be of a great importance.

Detection of drug-induced, superoxide-mediated cell damage and its prevention by antioxidants.

The mode of the cytotoxic activity of three benzo(c)fluorene derivatives was characterized. The observed morphological changes of lysosomes or variations of mitochondrial activity are assumed to be the consequence of cell protection against oxidative damage and/or the part of the damage process. To establish the relationship between the quantity of superoxide (O2*-) generated and the degree of damage resulting from O2*-, a simple system based on measurement of 3-(4-iodophenyl)-2-(4-nitrophenyl)-5-phenyltetrazolium chloride (INT) reductase activity in the presence of superoxide dismutase (SOD) was used. The functionality of the chosen battery of in vitro tests was proved using several known superoxide inducers: cyclosporin A (CsA) and benzo(a)pyrene (BP), as well as noninducers: citrinin (CT) and cycloheximide (CH). From the results followed that the cell growth tests are much better indices of toxicity than the other tests. The model system for the evaluation of the protective capacity of antioxidants against superoxide-induced cytotoxicity included simultaneous exposure of HeLa cells to cytotoxic drugs and to quercetin (Qe), an antioxidant of plant origin. The complete abolishment of the inhibition of cell proliferation and clonogenic survival was concluded to be due to the protective effect of the antioxidant. These observations correlated with the decrease of superoxide content as estimated by the INT-reductase assay in the presence of SOD using the same model system, as well as with the increase of intracellular SOD content and its activity.

Circulating advanced glycation end product levels in rats rapidly increase with acute renal failure.

BACKGROUND: Advanced glycation end products (AGEs) are formed on proteins and peptides slowly during aging, and they accumulate in circulation and tissues in diabetes and chronic renal failure. Except for nonenzymatic glycation, enhanced oxidative/carbonyl stress is supposed to participate in their formation. The kidney plays a key role in disposal of AGEs, particularly AGE-peptides. We assumed that even a short time combination of enhanced oxidative/carbonyl stress and a lack of renal function should result in elevation of circulating AGE levels. METHOD: To verify this hypothesis, two models of acute renal failure in rats, bilateral nephrectomy and bilateral ureteral ligation, were employed, and the data were compared with those of sham-operated animals. RESULTS: AGE levels determined fluorimetrically or as carboxymethyllysine concentration rose by a factor of three within 48 hours. Enhanced levels of malondialdehyde and lipofuscin pointed to an enhanced oxidative/carbonyl stress. Activity of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase were not compromised, or were even elevated, respectively. Total antioxidant status increased, probably as a consequence of an accumulation of indols and benzoic acid derivatives, uremic toxins with scavenging capacities, as shown for hippurate. CONCLUSIONS: Evidence was given that circulating AGEs in the model of acute renal failure in rats undergo a substantial rise within a short time period. A source of increased AGEs is not clear, since except for the lack of the kidney function, accelerated synthesis of AGEs under enhanced oxidative/carbonyl stress as well as liberation of AGEs from tissues due to protein catabolism might be anticipated. If AGEs accumulate in acute renal failure in humans, their contribution to acute toxicity, or of the development of the complications later, might be of importance.

Plasma levels of advanced glycation end products in children with renal disease.

In adults, advanced glycation end products (AGEs) rise slowly in tissues and circulation during aging, and accumulate at an accelerated rate both in diabetes and chronic renal insufficiency (CRI). We aimed to investigate the pattern of AGE accumulation in children/adolescents with CRI and on renal replacement therapy by dialysis and transplantation. Concentrations of fluorescent AGEs, carboxymethyllysine (CML) and lipofuscin-like substance (LFLS, a marker of lipid peroxidation) were followed. Data were obtained from 11 CRI patients on conservative treatment (age 12.6+/-1.7 years, serum creatinine: 205.7+/-17.5 micromol/l), ten patients on renal replacement therapy with dialysis (13.6+/-1.7 years, 698.2+/-48.9 micromol/l) and nine patients after kidney transplantation (15.9+/-1.1 years, 115.9+/-12.0 micromol/l) and comparison made with the data from 28 healthy controls (11.8+/-8.2 years, 44.1+/-8.2 micromol/l). In controls, an age-dependent rise of fluorescent AGE and CML levels was observed. In the CRI group, fluorescent AGEs [0.38+/-0.03x105 arbitrary units (AU)] and CML (369+/-26 ng/ml) concentrations were doubled compared with controls (0.16+/-0.03x105 AU and 189+/-42 ng/ml, respectively) and even higher levels were revealed in dialyzed patients (0.80+/-0.05x105 AU; 650+/-94 ng/ml). Successful kidney transplantation significantly reduced but did not normalize fluorescent AGE levels (0.39+/-0.03 x105 AU), while the decline in CML levels (550+/-47 ng/ml) was insignificant. Plasma LFLS was elevated in CRI (19.6+/- 1.7 AU) and was even higher in dialyzed children (32.0+/-5.3 AU) compared with healthy controls (7.1+/- 1.4 AU). Kidney transplantation did not normalize LFLS levels (20.3+/-5.3 AU), pointing to persistently enhanced lipid peroxidation. Our study provides the first data on enhanced fluorescent AGEs and CML levels in children/adolescents with CRI and on dialysis. Successful renal transplantation decreased but did not normalize AGE levels, probably because of still-impaired renal function with enhanced oxidative stress, as well as the influence of immunosuppressive therapy.

Malondialdehyde, lipofuscin and activity of antioxidant enzymes during physical exercise in patients with essential hypertension.

DESIGN: To clarify the role of oxidative damage in essential hypertension, levels of lipid peroxidation products (malondialdehyde and lipofuscin) and activity of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) were examined during a short period of physical exercise. PATIENTS AND METHODS: We studied 11 male patients with mild to moderate essential hypertension in World Health Organization classes I or II and 10 healthy male controls. Physical exercise was performed on a bicycle ergometer at graded intensities of 1.0, 1.5 and 2.0 W/kg body weight Plasma concentrations of lipofuscin, malondialdehyde, epinephrine, norepinephrine, insulin, free fatty acids and glucose were determined. Superoxide dismutase activity was analysed in erythrocytes and glutathione peroxidase activity in whole blood. RESULTS: Concentrations of lipofuscin and malondialdehyde were significantly elevated in hypertensive patients. Superoxide dismutase activity was not different between groups, while glutathione peroxidase activity was significantly decreased in hypertensive subjects. During exercise, the concentration of malondialdehyde and antioxidant enzyme activities increased significantly in both groups. No differences were found in absolute increases between the normotensive and hypertensive subjects. The levels of glucose, insulin and free fatty acids were similar in both groups. Basal concentrations of catecholamines and also the exercise-induced increases were lower in hypertensive patients. CONCLUSIONS: Our results indicate increased oxidative damage in patients with essential hypertension, which might be caused by a decrease in the activity of glutathione peroxidase. The ability of superoxide dismutase and glutathione peroxidase to respond to increased production of reactive oxygen species during a short period of physical exercise was not impaired in hypertensive subjects.