[Oxidation Stress Markers Dynamics in the Experiment of Long-Term Antiorthostatic Hypokinesia (Retrospective Study)].

In blood serum of 9 volunteers aged 27 to 42, participated in the experiment with 370-day antiorthostatic hypokinesia (-5 degrees), the lipid peroxidation derivates concentration--diene conjugates (DC), malonic dialdehyde (MDA), Schiff bases (SB) as well as antioxidant defense system indices--tocopherol (TP) concentration and total antioxidative activity level (AOA) were measured. The volunteers were divided into two groups subjected to physical training regimes and used prophylactic measures. In both groups the lipoperoxidation processes initial stages depression (by 54-73%) was observed starting from 50th day, thus the lipid peroxidation final product--SB level was decreased (by 50-61%) only to the 230 day and remains approximately at the same level till the end of the experiment. The restorative period was characterized by decreasing (in 1.6-2.3 times) of MDA and SB concentrations. The decrease in lotal AOA during the aftereffect period was detected in all volunteers, and its level was significantly lower physiological norm range. Probably, long-term adaptation to the simulated weightlessness conditions is accompanied by expressed decrease in biological oxidation processes intensity and significant stress effect, as indicates by essential depression of lipid free radical oxidation in the course of the experiment. At the same time the restorative period after 370-day antiorthostatic hypokinesia was characterized by significantly expressed and prolonged readaptation stress progress. It is evidenced by practically twofold decrease in lipoperoxidation processes intensity against significant increase in TP concentration and water-soluble antioxidants functional reserves exhaustion. Lipid peroxidation activation absence in all terms of examination reflects appropriate compensation of studying impact by volunteers.

Spectroscopic, electrochemical DNA binding and in vivo anti-inflammatory studies on newly synthesized Schiff bases of 4-aminophenazone.

4-Aminophenazone (Ap-1) Schiff bases i.e., 4-{(3,4,5-trimethoxybenzylidine) amino}phenazone (Ap-2), 4-{(2-chlorobenzylidine) amino}phenazone (Ap-3) and 4-{(4-chlorobenzylidine)amino} phenazone (Ap-4) were synthesized and characterized by different spectroscopic techniques. Interaction of these compounds with ds.DNA was investigated through UV-Visible spectroscopy, fluorescence spectroscopy and cyclic voltammetry at stomach (4.7) and blood (7.4) pH under 37 °C (human body temperature). Instrumental findings were further quantified both kinetically and thermodynamically. Results obtained through these techniques inferred intercalative mode of binding of all the compounds with DNA. The binding constant data, "Kb", and free energy change, ΔG, indicated comparatively greater binding affinity and more spontaneity of binding of compounds with DNA at stomach pH (4.7), respectively. However, among these compounds, Ap-4 showed comparatively greater binding at both the pH. Formation of compound-DNA complex was further confirmed through the decrease in diffusion rates after the addition of DNA. The in vivo anti-inflammatory activity of the compounds was evaluated using the carrageenan-induced hind paw edema method. The results revealed that among all the compounds, Ap-4 showed greater percentage of edema inhibition compared to standard drug.

[Biochemical markers of oxidative stress in different forms and phases of multiple sclerosis].

OBJECTIVE: To verify a role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and to develop oxidative stress prognostic criteria of disease course and treatment recommendations. MATERIAL AND METHODS: We examined 220 patients with different clinical forms and phases of MS. The lipid and protein free-radical oxidation markers were measured using the following parameters: ketodienes, diene conjugates, malondialdehyde, and Schiff bases. The functioning of the endogenous antioxidant defense system was assessed using y the activity of vitamin E, general and non-protein SH-groups, which represented the nonenzymatic segment of the antioxidant defense system. The enzymatic segment markers were superoxide dismutase, glutathione peroxidase, and glutathione reductase. RESULTS AND CONCLUSION: The findings revealed significant differences in the oxidative stress intensity indices in patients with different clinical forms and phases of MS, which made it possible to predict disease progression and prescribe the complex antioxidant treatment in the evidence-based practice.

[Redox-dependent processes in blood plasma, neutrophils and erythrocytes of patients with ovary cancer after polychemotherapy by CAP scheme].

The dynamics of the redox-dependent processes in blood plasma, neutrophils and erythrocytes of the patients with ovary cancer of the IIIrd clinical stage by FIGO after polychemotherapy according to the CAP scheme is considered. In the blood plasma and erythrocytes there were estimated the values of protein oxidative modification: carbonyl derivatives at λ = 346 nm, 370 nm, 430 nm and 530 nm; the lipid peroxidation parameters: malonic dialdehyde, dienic conjugates, ketodiens, shiff's bases; the fermentative chain of the antioxidant system: activities of catalase, glutationtransferase and superoxide dismutase. In the peripheral blood neutrophils there were cytochemically determined the myeloperoxidase activity and the number of the active neutrophils in the spontaneous NBTR-test. After the polychemotherapy there were detected higher levels of the protein oxidative modification products and the products of the lipid peroxidation in the blood plasma and erythrocytes of the patients. Simultaneous increase of the activity of the antioxidant enzymes in the blood plasma could be evident of a high level of the lipid antioxidants peroxidation system functioning, whereas the simultaneous decrease of the activity of the antioxidant enzymes in the erythrocytes was indicative of passible development of oxidative stress in them. After the chemotherapy there was observed a significant and reliable decrease of the total number of the neutrophils. After the second course of the chemotherapy the activity of myeloperoxidase in them in the spontaneous NBTR-test as well decreased. Such a dynamics of the redox-depended processes in various components of the blood in the tumour carrier was characteristic of the tumor biological picture and required the use of differential multicomponent antioxidant therapy in patients with ovary cancer.

Effect of chemotherapy on serum end-products of lipid peroxidation in patients with small cell lung cancer: association with treatment results.

Many anti-cancer drugs induce formation of lipid peroxidation products that are toxic for lung cancer cells in vitro. We tested whether changes of serum thiobarbituric acid reactive substances (TBARs) and Schiff's bases (SB) are associated with treatment efficacy in 37 small cell lung cancer (SCLC) patients. Subjects received carboplatin (350 mg/m2, i.v.-Day 1), vincristine (1.3 mg/m2, i.v.-Day 1), and etoposide (120 mg/m2, oral dose-Days 1-4). Then 5 subsequent cycles were repeated at 21-day intervals. Serum TBARs and SB were measured fluorimetrically before and 6, 24h after introduction of the 1st, 3rd and 6th cycles. TBARs and SB levels rose 24 h after 1st chemotherapy in the whole group (2.5+/-1.4 vs. 4.2+/-2.0 micromol/dl, P<0.001 and 26.3+/-16.7 vs. 29.7+/-9.8U(430)/ml, P<0.01, respectively) and the highest increments were in 19 patients with complete or partial response after 1st, 3rd and 6th cycles. In 9 subjects with progressive disease occurring before the 2nd cycle (early progression) TBARs and SB decreased 6 and 24h after the 1st cycle (4.3+/-1.2 vs. 3.4+/-1.4, P<0.05 vs. 2.7+/-0.9 micromol/dl, P<0.05 and 50.2+/-17.0 vs. 36.7+/-13.2, P<0.05 vs. 36.5+/-13.4 U(430)/ml, P<0.01, respectively). Patients survival correlated with the 1st cycle-induced TBARs (r=0.49, P<0.001) and SB (r=0.56, P<0.002) increments. Subjects with negative SB and TBARs increments (n=8) had shorter survival than those (n=29) with positive increments in lipid peroxidation products (log rank test P<0.005). Monitoring of circulatory TBARs and SB may be helpful for screening of SCLC patients with high risk of early disease progression and chemotherapy failure.

Effect of nitroglycerin on some parameters of the prooxidant-antioxidant balance and functional state of the liver during ischemia/reperfusion.

The effect of nitroglycerine on some parameters of the prooxidant-antioxidant balance and functional state of the liver under conditions of ischemia/reperfusion was studied on rabbits. Hepatic ischemia/reperfusion was accompanied by accumulation of LPO products, depletion of the antioxidant defense system, and increase in blood transaminase activity. Nitroglycerine infusion before the reperfusion period decreased the concentration of LPO products, increased activity of the antioxidant system, and improved liver function.

Influence of different oxygen modes on the blood oxygen transport and prooxidant-antioxidant status during hepatic ischemia/reperfusion.

Oxygen supply was corrected in rabbits during the hepatic ischemia/reperfusion by means of different breathing mixtures: hypoxic (14.8 % O(2)+85.2 % N(2)), hyperoxic (78 % O(2)+20.2 % N(2)+ 1.8 % CO(2)), or hypercapnic (5 % CO(2) in air). Hepatic ischemia was induced for 30 min by ligation of hepatic artery, reperfusion period lasted 120 min. Indices of blood oxygen transport (p50(act), pCO(2), pH, pO(2), etc.) and prooxidant-antioxidant balance (Schiff bases, conjugated dienes, catalase, retinol, alpha-tocopherol) were measured in the blood and liver. The severity of reperfusion damage was evaluated by the activities of alanine and aspartate aminotransferases (ALT, AST) in the blood. Hepatic ischemia/reperfusion resulted in higher p50(act) in hepatic venous and mixed venous blood in all experimental groups. The changes of p50(act) were most marked in the hypercapnic group and were the weakest in the hypoxic group. The rise in p50(act) was accompanied by higher levels of lipid peroxidation products, ALT and AST in blood and liver homogenates, and by a simultaneous fall of alpha-tocopherol and retinol concentrations, except in the hypoxic group. Catalase activity at the end of reperfusion increased under normoxia, decreased under hyperoxia or hypercapnia and did not change under hypoxia. The moderate hypoxia during reperfusion was accompanied by a better balance between the mechanisms of reactive oxygen species production and inactivation that may be observed by optimal changes in p50act and reduced the hepatic damage in this pathological condition.

[Clinical and biochemical aspects of flixotide administration in patients with moderate bronchial asthma]. / Kliniko-biokhimicheskie aspekty primeneniia fliksotida u bol'nykh bronkhial'noi astmoi srednetiazhelogo techeniia.

AIM: To compare clinical, device and biochemical aspects of monotherapy with flixotide vs combination of flixotide with serevent in patients with moderate bronchial asthma (MBA). MATERIAL AND METHODS: 18 patients with MBA received flixotide and 18 MBA patients flixotide plus serevent for two weeks of lead-in and eight weeks of basic treatment. A special study was made of neutrophils which were examined for activity of LPO-antioxidants and phospholipid spectrum of membranes. RESULTS: There were similar changes in function of the system LPO-antioxidants and lipid structure in neutrophilic membranes of moderate BA patients of both the groups. CONCLUSION: Clinicobiochemical efficacy of mean doses of a new topic inhalation glucocorticoid flixotide alone or in combination with prolonged beta 2-adrenostimulator serevent is demonstrated. There were positive trends in metabolic processes in neurophilic membrane. Use of flixotide in combination with serevent is clinically preferable.

Analysis of the relationship between hemoglobin-oxygen affinity and lipid peroxidation during fever.

Endogenous hyperthermia was induced in rabbits by i.v. pyrogenal administration. Hemoglobin-oxygen affinity and parameters of free radical lipid oxidation in plasma and red blood cells were measured. The content of diene conjugates, malonic dialdehyde and Schiff bases were determined at a pyrogenal dose of 4 minimal pyrogenic doses/kg, and iron-initiated chemiluminescence, catalase activity and alpha-tocopherol concentration were determined at 6 minimal pyrogenic doses/kg. A rightward shift of the real oxyhemoglobin dissociation curve and activation of lipid peroxidation were observed. Relationships between the parameters measured were analyzed. Decreased hemoglobin-oxygen affinity is considered to be a possible mechanism of activation of free radicals during fever.

Effect of alcohol consumption on blood antioxidant nutrients and oxidative stress indicators.

The effects of alcohol consumption on plasma concentrations of antioxidant vitamins (alpha-tocopherol and ascorbic acid), selenium, and markers of oxidative stress, especially malondialdehyde (MDA) and autoantibodies directed to MDA adducts to proteins (Ig-NH2-MDA) were investigated in a large population of 417 supposedly healthy men who consumed only low or moderate amounts of alcohol as compared with 102 alcoholic patients without severe liver disease, who were studied both before and after 21 d of withdrawal treatment. Plasma concentrations of alpha-tocopherol, ascorbic acid, and selenium were lower in alcoholics than in men who drank low amounts of alcohol (P < or = 0.001), whereas MDA and Ig-NH2-MDA were higher (P < or = 0.001). Plasma concentrations of alpha-tocopherol and selenium remained unchanged after the withdrawal period, whereas ascorbic acid (P < or = 0.01), MDA, and Ig-NH2-MDA concentrations decreased (P < or = 0.001). Adjustment of data for circulating lipids and nutritional intake suggests a specific effect of alcohol on antioxidant vitamins, independent of nutritional status.

[The characteristics of the regulation of blood lipid peroxidation in acute pneumonia and acute pneumonia combined with diabetes mellitus]. / Osobennosti reguliatsii perekisnogo okisleniia lipidov krovi pri ostroi pnevmonii i pri ostroi pnevmonii v sochetanii s sakharnym diabetom.

The changes in the levels of diene conjugates, Schiff bases and malonic dialdehyde were followed up in red blood cells and plasma of 178 acute pneumonia (AP), diabetes mellitus (DM) and AP+DM patients. The findings for AP and AP+DM were compared to acute-phase indices of the inflammation and clinical pattern. The blood of the patients was endovascularly exposed to low-energy He-Ne laser irradiation. The resultant trends in LPO were recorded. It is concluded that by changes in the concentrations of diene conjugates, Schiff bases and malonic dialdehyde one can judge on the course of the above diseases and evaluate efficacy of on-going treatments, eg. He-Ne laser, antioxidants.

[The correlation between the activity of free-radical peroxidation and erythrocyte hemolysis in experimental thermal trauma]. / Korelatsionna zavisimost mezhdu aktivnostta na svobodno-radikalnoto prekisno okislenie i khemolizata na eritrotsitite pri eksperimentalna termichna travma.

Increased concentration of the products of red-cell free-radical oxidation (FRO), i.e. of malondialdehyde (MDA) and of Schiff bases in red cells and of their hemolysis was recorded in the acute period of experimental thermic injury. Alpha-tocopherol applied after thermic injury suppressed FRO and restricted red cell hemolysis. A strong positive correlation was recorded between hemolysis and MDA (r = 0.97) and between hemolysis and Schiff bases (r = 0.88). This high-grade positive correlation between hemolysis and content of secondary and end products of FRO, as well as their decrease after alpha-tocopherol treatment give grounds to admit that activated peroxidation processes in red cells play a definite role for destabilization of their membranes. The role of hemolysis for secondary FRO activation and for implication of the whole organism in the overall pathologic process, the burn disease, is discussed.

Erythrocyte rheology and lipid peroxidation in burns.

Alterations in the erythrocyte rheology and the contents of activated free radical oxidation products (conjugated dienes, products of thiobarbituric acid and Schiff bases) in the acute phase of experimental thermic injury of the skin were studied. Erythrocyte flexibility reduction and erythrocyte aggregation increase correlated with elevated amounts of free radical oxidation products. Alpha-tocopherol avoided the accumulation of free radical oxidation products and improved both antioxidant defence and erythrocyte rheology. Thus we suppose that free radical oxidation products probably participate in the pathogenesis of erythrocyte rheology disturbances after thermic trauma.

[The effect of parmidine on the lipid peroxidation processes in coronary atherosclerosis]. / Vliianie parmidina na protsessy perekisnogo okisleniia lipidov pri koronarnom ateroskleroze.

During the formation and development of atherosclerosis the intensity of lipid peroxidation and the activity of antioxidant defence system significantly change. The use of parmidine decreases the contents of primary and secondary products of lipid peroxidation, reduces peroxide hemolysis of erythrocytes and increases the content of reduced glutathione in erythrocytes of patients with atherosclerosis. This shows that parmidine possessing the antioxidant properties stabilizes lipid peroxidation processes and normalizes the physiological antioxidant system.

[Effect of tranquilizers on lipid peroxidation of biological membranes]. / Vliianie trankvilizatorov na perekisnoe okislenie lipidov biologicheskikh membran.

Thirty-seven patients with unstable angina pectoris were treated with prolonged-action nitrates for 20 days; 8 of these received additionally meprobamate in a dose of 0.4 g per day and 11 patients received phenazepam in a dose of 0.002 g per day. The addition of tranquillizers to the complex of treatment led to a significant decrease of one of the final products of biological membrane lipid peroxidation--Schiff's bases in erythrocytic membranes. During treatment with phenazepam a similar decrease was more rapid (by the 5th day of treatment) and more pronounced.

[Activation of lipid peroxidation in the bodies of schizophrenic and manic-depressive patients]. / Aktivatsiia perekisnogo okisleniia lipidov v organizme bol'nykh shizofreniei i maniakal'no-depressivnym psikhozom.

The intensity of lipid peroxidation was studied in schizophrenic and manic-depressive patients. Peroxidation was found to be activated in these diseases as assessed by the content of peroxidation products in the lipid fraction of blood plasma. Manic-depressive patients showed a significant decrease in the intensity of peroxidation processes with improvement in the clinical symptoms of the disease.

[Alpha-tocopherol in the complex treatment of several forms of epilepsy]. / Al'fa-tokoferol v kompleksnoi terapii nekotorykh form épilepsii.

Seventeen patients with various forms of epilepsy who had shown resistance to the routine anticonvulsant and psychotropic therapy were treated with alpha-tocopherol (600 mg once daily). Prior to the tocopheral treatment all patients showed pathological changes on the electroencephalogram (EEG) and a two to ten-fold increase in the plasma levels of lipid peroxidation (LPO) products. A beneficial effect was observed in all patients one month after the drug administration. In 11 cases, it was accompanied by decreased blood levels of LPO products and by positive changes on the EEG. The clinical action of alpha-tocopherol was manifested first in the appearance of adequate emotional-volitional activity and then in a reduced frequency of epileptic seizures. In four patients, generalized seizures were arrested completely. In five cases, the treatment did not affect the blood content of LPO products, although the prevalence and severity of affective phenomena were reduced. Thus, the inclusion of alpha-tocopherol into the multiple modality therapy of certain forms of epilepsy raises the efficacy of its treatment.

Mechanism and speed of reactions between haemoglobin and glucose consequences for the measurement of glycosylated haemoglobins in patient material.

The mechanism of the reactions between haemoglobin and glucose in the erythrocyte was investigated in vitro using 14C-labelled glucose. Reaction speed constants were found for the formation of HbA1c (4.2 . 10(-3) and the formation and degradation of the Schiff Base (9.22 . 10(-4) and 0.435, respectively) for concentrations in mmol/l and time in hours at 37 degrees C. An equilibrium constant of 2.12 . 10(-3) was found for the reversible formation of the Schiff Base. The results were included in a mathematical model with which a number of clinically relevant situations were simulated. From the results the conclusion was drawn that during the measurement of fast haemoglobins, the intermediate Schiff Base causes a variation dependent on the glucose concentration at the moment of blood sampling. The model demonstrates that this disturbance can be eliminated by incubating erythrocytes with physiological saline for 10 h at 37 degrees C.