State of lipid peroxidation,blood antioxidant defense in patients with myocardial infarction aggravated by circulatory insufficiency

AIM: To study free radical processes in patients with myocardial infarction (MI) aggravated by heart failure. MATERIAL AND METHODS: Forty seven patients taken to the clinic within the first 5 hours of MI were examined. The patients were divided into 2 groups: 1) those with left ventricular failure-complicated IM (n = 25); 2) those with uncomplicated MI (n = 22). A control group included 17 apparently healthy males. The activity of lipid peroxidation (LPO) and blood antioxidative defense was determined in the patients' red blood cells prewashed off the plasma with saline solution at a temperature of 4 degrees C. RESULTS: The tension of free radical lipid oxidation mechanisms in patients with MI aggravated by circulatory insufficiency is followed by an increased antiradical activity. In patients with uncomplicated higher LPO activity is attended the less marked activation of antioxidative enzymes. The examinees were found to show a correlation of the global systolic function of the left ventricle with the concentration of LPO products and with the activity of antioxidative enzymes. CONCLUSION: More significant LP activation coupled with left ventricular systolic dysfunction was noted in patients with MI aggravated by acute heart failure.     

Effect of hyperbaric oxygenation on free-radical processes and gastric acid production in patients with duodenal ulcer

Ascorbate- and NADPH-dependent free radical oxidation, the state of the antioxidant system, hydrogen iron secretion rate (HISR) and acid production kinetic function (AFKF) were investigated in 38 patients with duodenal ulcer to study the effect of hyperbaric oxygenation on free radical processes and gastric acid production. Assessment of the results of the study indicated the activation of NADPH-dependent free radical lipid oxidation, HISR acceleration and AFKF enhancement during hyperbaric oxygenation in the treatment of duodenal ulcer which required adjuvant corrective therapy.     

Blood lipids and intensity of free radical oxidant processes in elderly patients with ischemic heart disease on antiatherogenic vegetarian diet

The authors studied the effects of balanced antiatherogenic vegetarian diet enriched with soya bean products on blood lipids and intensity of free radical oxidant processes in elderly patients with ischemic heart disease. 45 patients with dyslipoproteinemia type IIA or IIB were examined for hemodynamic parameters, lipid spectrum and intensity of free radical oxidation. The diet promoted a trend to normalization of central hemodynamics, significantly reduced the level of atherogenic lipids in blood, improved free radical lipid peroxidation and activity of nonenzymatic antioxidant defence.     

C18 hydroxy fatty acids as markers of lipid peroxidation ex vivo and in vivo

Different C18 monohydroxy fatty acids (OHFAs) were evaluated for their usefulness as markers of plasma lipid peroxidation (unsaturated fatty acid oxidation) ex vivo and in vivo. First, plasma samples (n = 5) were exposed for 3 h to different radical fluxes ex vivo. The formation of OHFAs was assessed by using varying concentrations of Cu2+ ions and AAPH (2,2'-azobis(2-amidinopropane) hydrochloride) as radical flux initiators. Secondly, a cross-sectional study was carried out in 47 middle-aged men. In this study, plasma concentrations of different in vivo OHFAs were compared with other indices of lipid peroxidation. Under mild oxidation conditions (heparin plasma containing 4.2 or 8.3 mM AAPH), concentrations of all the measured OHFAs (8, 9, 10, 11, 12, 13, 15 and 16-OH acids) increased in an identical manner, but under highly oxidative conditions (heparin plasma containing 83 mM AAPH or 4.2 to 8.3 mM CuSO4) mainly 9 and 13-OHFAs were formed. In the cross-sectional study, plasma 11 and 13-OHFA levels were associated statistically significantly with plasma free F2alpha-isoprostanes, recognized index of in vivo lipid peroxidation (r = 0.305, p = 0.037 and r = 0.308, p = 0.035, respectively). In addition, 16-OHFA levels correlated with the ratio of electronegatively charged LDL to total LDL (r = 0.335, p = 0.021). With respect to the other OHFAs, 15-OHFA had no correlation with either other OHFAs or the reference substances used. In addition, occasionally there were contamination problems in the assessment of 12-OHFA. It is concluded that all of the measured C18 OHFAs can be used as indicators of plasma lipid peroxidation under mild oxidation conditions, though the 12 and 15-OHFAs may need to be used with some caution. Under high oxidation conditions, 9-and 13-OHFAs seem to be the most useful indices because of their high formation capacity.     

The generation of active forms of oxygen by the blood leukocytes, lipid peroxidation and antiperoxide protection in bronchial asthma patients]

A study was made of the generation of active forms of oxygen by leukocytes, of free radical lipid peroxidation and antiperoxide activity (APA) in 52 bronchial asthma (BA) patients depending on the disease phase and of a possibility of their correction with antioxidants. In BA exacerbation, chemiluminescence of leukocytes (CL) and plasma content of malonic dialdehyde (MDA) increase whereas plasma APA reduces as compared to the control. During remission, CL and plasma content of MDA decrease but do not reach normal. Simultaneously one can see a tendency toward plasma APA reduction as compared with the phase of exacerbation. BA patients who received antioxidants in addition to the conventional therapy demonstrated a more pronounced lowering of CL and plasma MDA content than those given the conventional therapy alone. The data obtained attest to the activation of free radical oxygen and lipid processes and to inhibition of plasma APA in BA, providing evidence in favour of including antioxidants in combined therapy of BA.     

Clinical assessment of lipid free-radical oxidation in chronic glomerulonephritis patients

A study was made of peroxidation of lipids of erythrocytic biomembranes in 42 patients with chronic glomerulonephritis: 23 patients with the urinary syndrome and 19 with the nephrotic syndrome. Activation of free radical lipid oxidation was shown in both groups of patients; it was especially marked in the group with the nephrotic syndrome. Three degrees of the activity of a renal process were defined on the basis of difference in the concentration of secondary peroxidation products in concrete patients. Correlation between lipid peroxidation indices and expression of proteinuria and leukocyturia was established.     

Assessment of adipose tissue metabolism by means of subcutaneous microdialysis in patients with sepsis or circulatory failure

To evaluate the role of adipose tissue in the metabolic stress response of critically ill patients, the release of glycerol and lactate by subcutaneous adipose tissue was assessed by means of microdialysis in patients with sepsis or circulatory failure and in healthy subjects. Patients with sepsis had lower plasma free fatty acid concentrations and non-significant elevations of plasma glycerol concentrations, but higher adipose-systemic glycerol concentrations gradients than healthy subjects or patients with circulatory failure, indicating a stimulation of subcutaneous adipose lipolysis. They also had a higher lipid oxidation. Lipid metabolism (adipose-systemic glycerol gradients, lipid oxidation) was not altered in patients with circulatory failure. These observations highlight major differences in lipolysis and lipid utilization between patients with sepsis and circulatory failure. Hyperlactataemia was present in both groups of patients, but the adipose-systemic lactate concentration gradient was not increased, indicating that lactate production by adipose tissue was not involved. This speaks against a role of adipose tissue in the development of hyperlactataemia in critically ill patients.     

Variations in thyroid function and sleep in healthy young men.

1. The total serum thyroxine, tri-iodothyronine resin uptake, total plasma protein concentration and the free thyroxine index (FTI) were determined repeatedly, at 07.15, 13.00 and 22.30 hours over 4 days, in six healthy young men. 2. There was a significant diurnal variation in the total serum thyroxine concentration but this reflected changes in the binding capacity of serum proteins and in the total plasma protein concentration which could be explained by changes of posture. The FTI, and presumably therefore the free thyroxine concentration, varied very little with the time of day. 3. The FTI varied significantly from day to day in three of the six subjects, presumably as a result of changes in thyroxine secretion because the serum binding capacity did not vary. 4. The subjects' sleep at night was assessed by electro-encephalogram. In days when the FTI was highest for a particular subject his sleep was more fragmented by spontaneous awakenings, the amount of rapid-eye-movement sleep was reduced and that of delta-wave sleep was increased, implying that variations in thyroid function over a period of a few days in healthy subjects can be of physiological significance. The cause of these variations is uncertain.     

Screening for minimal hypothyroidism. How sensitive is the free thyroxine assay?

The free thyroxine index (FTI) and a free thyroxine (FT4) assay were compared with the thyrotropin-releasing hormone stimulation test in 98 consecutive patients to determine whether the FT4 assay is more sensitive than the FTI in screening patients for minimal hypothyroidism. FTI and FT4 values did not agree with the clinical evaluation in 20% (3/15) of the patients with a transitional thyroid-stimulating hormone (TSH) response (21 to 35 microU/ml) and in 64.3% (9/14) of the patients with an augmented TSH response (greater than 35 microU/ml). From these results we conclude that the FT4 assay is no more sensitive than the FTI in detection of such minimal thyroid dysfunction.     

Clinical and laboratory evaluation of four methods of assessing free thyroxine status in thyroid clinic patients

The clinical value of four laboratory methods of assessing free thyroxine status was compared in 82 consecutive patients newly referred to a thyroid clinic with suspected thyroid dysfunction. The methods of determining free thyroxine used were: (1) free thyroxine index using a thyroid hormone uptake test (FTI (THUT)); (2) a free thyroxine index using thyroxine binding globulin (FTI (TBG)); (3) a kinetic radioimmunoassay (Immophase); and (4) an equilibrium dialysis method. The definitive thyroid status was evaluated by a combination of clinical assessment (including Wayne index), routine tests of thyroid function (total T4, T3, TSH, and TRH tests where appropriate), and by therapeutic trial in one case. The diagnostic efficiency of the tests was markedly dependent upon the method of determining the reference range for euthyroid patients. Best efficiency for each test was achieved using an amended range after excluding outliners. Test efficiency was then 97.6% for FTI (THUT) and the kinetic RIA and 96.8% for FTI (TBG). Misclassification by one or more of these tests occurred in only four patients (mild hypothyroid, euthyroid on phenytoin, euthyroid on oral contraceptive and valium, T3 hyperthyroid). In contrast, free T4 by equilibrium dialysis was much less efficient (86.6%) and was technically the most complex. Overall the kinetic T4 RIA provided similar diagnostic information to the indirect indices. However, further studies of cost benefit in settings other than a thyroid clinic are required to assess whether this method might replace total T4 and/or FTI as a first-line test of thyroid function.     

An evaluation of a fluorescence polarization immunoassay of thyroxin and thyroxin-uptake

We evaluated the fluorescence polarization immunoassay for total thyroxin (T4) and thyroxin-uptake (T-U) in the Abbott "TDx" Analyzer. Between-assay precision was good when we did once-fortnightly calibration and assayed samples in singleton. Measured T4 concentration was decreased in hemolyzed samples with obvious red coloration and undetectable in severely hemolyzed samples. The T-U assay was unaffected by hemolysis. Unlike the triiodothyronine-uptake methods, the T-U assay utilizes labeled T4 and measures a variable related to serum thyroxin-binding capacity rather than the concentration of unoccupied binding sites in serum. The T4 and T-U values of 422 samples correlated highly with a T4 (in-house) radioimmunoassay and a commercial assay for thyroxin-binding globulin, respectively. The free thyroxin ratio (ratio of T4 to T-U, FTI) correlated highly with free T4 concentration as measured by T4-analog-tracer radioimmunoassay (fT4 analog RIA). FTI and fT4 values were discordant in late pregnancy (normal FTI and low fT4) and euthyroid sick patients (above-normal or normal FTI and low fT4), suggesting that the FTI gives fewer misleading results in these patients.     

Localization of the oxidative defect in phytanic acid degradation in patients with refsum''s disease

The rate of oxidation of phytanic acid-U-(14)C to (14)CO(2) in three patients with Refsum's disease was less than 5% of that found in normal volunteers. In contrast, the rate of oxidation of alpha-hydroxyphytanic acid-U-(14)C and of pristanic acid-U-(14)C to (14)CO(2), studied in two patients, while somewhat less than that in normal controls, was not grossly impaired. These studies support the conclusion that the defect in phytanic acid oxidation in Refsum's disease is located in the first step of phytanic acid degradation, that is, in the alpha oxidation step leading to formation of alpha-hydroxyphytanic acid.The initial rate of disappearance of plasma free fatty acid radioactivity after intravenous injection of phytanic acid-U-(14)C (t(1/2) = 5.9 min) was slower than that seen with pristanic acid-U-(14)C (t(1/2) = 2.7 min) or palmitic acid-1-(14)C (t(1/2) = 2.5 min). There were no differences between patients and normal controls in these initial rates of free fatty acid disappearance for any of the three substrates tested.There was no detectable lipid radioactivity found in the plasma 7 days after the injection of palmitic acid-1-(14)C or pristanic acid-U-(14)C in either patients or controls. After injection of phytanic acid-U-(14)C, however, the two patients showed only a very slow decline in plasma lipid radioactivity (estimated t(1/2) = 35 days), in contrast to the normals who had no detectable radioactivity after 2 days. Incorporation of radioactivity from phytanic acid-U-(14)C into the major lipid ester classes of plasma was studied in one of the patients; triglycerides accounted for by far the largest fraction of the total present between 1 and 4 hr.     

C18 hydroxy fatty acids as markers of lipid peroxidation ex vivo and in vivo

Different C18 monohydroxy fatty acids (OHFAs) were evaluated for their usefulness as markers of plasma lipid peroxidation (unsaturated fatty acid oxidation) ex vivo and in vivo. First, plasma samples (n=5) were exposed for 3?h to different radical fluxes ex vivo. The formation of OHFAs was assessed by using varying concentrations of Cu²⁺ions and AAPH (2,2′‐azobis(2‐amidinopropane) hydrochloride) as radical flux initiators. Secondly, a cross‐sectional study was carried out in 47 middle‐aged men. In this study, plasma concentrations of different in vivo OHFAs were compared with other indices of lipid peroxidation. Under mild oxidation conditions (heparin plasma containing 4.2 or 8.3?mM AAPH), concentrations of all the measured OHFAs (8, 9, 10, 11, 12, 13, 15 and 16‐OH acids) increased in an identical manner, but under highly oxidative conditions (heparin plasma containing 83?mM AAPH or 4.2 to 8.3?mM CuSO₄) mainly 9 and 13‐OHFAs were formed. In the cross‐sectional study, plasma 11 and 13‐OHFA levels were associated statistically significantly with plasma free F_2α‐isoprostanes, recognized index of in vivo lipid peroxidation (r=0.305, p=0.037 and r=0.308, p=0.035, respectively). In addition, 16‐OHFA levels correlated with the ratio of electronegatively charged LDL to total LDL (r=0.335, p=0.021). With respect to the other OHFAs, 15‐OHFA had no correlation with either other OHFAs or the reference substances used. In addition, occasionally there were contamination problems in the assessment of 12‐OHFA. It is concluded that all of the measured C18 OHFAs can be used as indicators of plasma lipid peroxidation under mild oxidation conditions, though the 12 and 15‐OHFAs may need to be used with some caution. Under high oxidation conditions, 9‐and 13‐OHFAs seem to be the most useful indices because of their high formation capacity.     

类风湿关节炎患者血浆对氧磷酯酶-1活性与氧自由基代谢水平的相关性研究

目的探讨类风湿关节炎(RA)患者血浆对氧磷酯酶-1(PON-1)活性与氧自由基代谢水平的关系。方法检测118例RA患者和56名健康对照者血浆PON-1活性、氧化修饰低密度脂蛋白(ox-LDL)、丙二醛(MDA)含量、超氧化物歧化酶(SOD)和循环谷胱苷肽过氧化物酶(GSH-Px)活性及晚期蛋白质氧化产物(AOPP)水平,分析PON-1活性与氧自由基代谢水平的关系。结果RA患者血浆PON-1、SOD、GSH-Px活性分别为(122.2±24.1)kU/L、(78.2±21.3)kU/L、(156.4±32.2)U/L,低于对照组(P<0.01)。ox-LDL、AOPP、MDA水平分别为(832.0±256.2)μg/L、(342.3±118.1)μmol/L、(16.2±6.4)μmol/L,高于对照组(P<0.01)。RA患者血浆PON-1活性与GSH-Px、SOD呈正相关(r=0.781,P<0.01;r=0.702,P<0.01),与ox-LDL、MDA、AOPP呈负相关(r=-0.721,P<0.01;r=-0.789,P<0.01;r=-0.679,P<0.01)。结论RA患者血浆PON-1活性降低,...     

Formation of non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in plasma and low density lipoprotein exposed to oxidative stress in vitro.

F2-isoprostanes are prostaglandin F2-like compounds that are known to be formed in vivo by free radical oxidation of arachidonyl-containing lipids, and their plasma levels have been suggested as indicators of in vivo oxidative stress. As oxidation of LDL, a likely causal factor in atherosclerosis, involves lipid peroxidation, we investigated whether F2-isoprostanes are formed in plasma and LDL exposed to oxidative stress, and how F2-isoprostane formation is related to endogenous antioxidant status. In plasma exposed to aqueous peroxyl radicals, lipid hydroperoxides and esterified F2-isoprostanes were formed simultaneously after endogenous ascorbate and ubiquinol-10 had been exhausted, despite the continued presence of urate, alpha-tocopherol, beta-carotene, and lycopene. In isolated LDL exposed to aqueous peroxyl radicals or Cu2+, consumption of endogenous ubiquinol-10 and alpha-tocopherol was followed by rapid formation and subsequent breakdown of lipid hydroperoxides and esterified F2-isoprostanes, and a continuous increase in LDL's electronegativity, indicative of atherogenic modification. In Cu(2+)-exposed LDL, the decrease in esterified F2-isoprostane levels was paralleled by the appearance of free F2-isoprostanes, suggesting that hydrolysis by an LDL-associated activity had occurred. Our data suggest that F2-isoprostanes are useful markers of LDL oxidation in vivo. As F2-isoprostanes are potent vasoconstrictors and can modulate platelet aggregation, their formation in LDL demonstrated here may also have important implications for the etiology of cardiovascular disease.     

Protein oxidation biomarkers in plasma of type 2 diabetic patients

ObjectivesTo evaluate oxidative stress and the extent of oxidation of plasma proteins in type 2 diabetic patients.Design and methodsStudy was carried out on blood from 31 diabetic patients of both sexes (mean age = 58 ± 7; duration of diabetes 12 ± 5 years) and healthy age and sex matched normal subjects. Biomarkers of protein oxidation; plasma protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and –SH group and free radical scavenging capacity of plasma was measured.ResultsPCO and AOPPS levels were significantly (P < 0.005) higher in diabetic patients in comparison to healthy volunteers. Reduced free radical scavenging capacity (P < 0.001) and –SH group (P < 0.05) was observed in plasma of type 2 diabetic patients.ConclusionsOur data suggest that diabetics are susceptible to protein oxidation. Oxidative modulation of proteins due to reduced radical scavenging activity of plasma patients may be one of the reasons of altered physiological processes in type 2 diabetic patients.     

Relation between features of the psychoemotional status and lipid metabolism of patients with ischemic heart disease and arrhythmias

Interrelationship of the peculiarities of the psychoemotional status, the activity of lipid peroxidation and the content of blood free fatty acids were studied in 64 CHD patients with arrhythmia. It was shown that prolonged and pronounced psychoemotional strain, high levels of the activity of free radical lipid oxidation and the content of nonesterified fatty acids in the blood of CHD patients promoted the development of cardiac rhythm disturbances, particularly of ventricular extrasystoles. Patients with the psychoemotional strain syndrome demonstrated direct correlation of an induced initial hemiluminiscence flash value and the level of a psychological pattern MMPI by scales 2, 6, 7, 0, as well as close direct correlation of the concentration of free fatty acids with scales 6, 8, F and negative correlation with scale 3. The detection of the psychoemotional strain syndrome in CHD patients, especially in combination with high levels of lipid peroxidation and nonesterified fatty acids in the blood, may evidently serve an important criterion for defining patients at high risk of developing arrhythmias.     

Evaluation of the atherogenic tendency of lipids and lipoprotein content and their relationships with oxidant-antioxidant system in patients with psoriasis

BACKGROUND: Psoriasis is a common chronic and recurrent inflammatory skin disease that can occur due to abnormalities in essential fatty acid metabolism, lymphokine secretion, free radical generation, lipid peroxidation and eicosanoid metabolism, and has been associated with increased frequency of cardiovascular events. The current study was designed to evaluate plasma lipids, susceptibility of LDL to oxidation and oxidant-antioxidant status and their relationships in patients with psoriasis. METHODS: The study group included 35 patients with psoriasis (18 females and 17 males), and 35 sex- and age-matched healthy volunteers (16 females and 19 males). From blood samples, their lipids, lipoproteins, acute phase reactants, lipid peroxidation products [lipid hydroperoxide (LHP) and malondialdehyde (MDA)], antioxidant enzymes [glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT)], total antioxidant status (TAS) and autoantibodies against oxidized low-density lipoprotein (AuAb-oxLDL) levels were determined. Moreover, the susceptibility of copper-induced in vitro oxidation of LDL was examined. RESULTS: The mean levels of atherogenic lipids (total cholesterol [TC], triacylglycerol [TG] and LDL cholesterol [LDL-C]), acute-phase reactants (CRP, ESR, PMNLs, ceruloplasmin and fibrinogen) and lipid peroxidation products, AuAb-oxLDL levels in patients with psoriasis were found to be significantly higher than those of healthy subjects. On the other hand, TAS and antioxidant enzyme activities (CAT, SOD and GSH-Px in erythrocyte and SOD in plasma) were significantly lower when compared to healthy subjects. The lag times [t(lag)], a measure of resistance to oxidation of LDL, were also lower. The levels of AuAb-oxLDL in patients were correlated with TC, LDL-C, plasma LHP, erythrocyte MDA, oxidized LDL-MDA (oxLDL-MDA), fibrinogen, CRP, PMNL levels and plasma SOD activities (r = 0.69, P < 0.01; r = 0.64, P < 0.01; r = 0.38, P < 0.05; r = 0.65, P < 0.01; r = 0.34, P < 0.05; r = 0.34, P < 0.05; r = 0.53, P < 0.01, r = 0.34, P < 0.05; r = -0.67, P < 0.01, respectively). On the other hand, t(lag) was correlated negatively with the levels of VLDL-TG, VLDL-TC and LDL-TG but positively correlated with the levels of TAS in psoriatics (r = -0.49, P < 0.01; r = -0.49, P < 0.01, r = -0.65, P < 0.05; r = 0.37, P < 0.05). CONCLUSIONS: It was concluded that the psoriatic patients could be considered as a group with an increased atherosclerotic risk because of increased oxidant stress, decreased antioxidant capacity and susceptibility in lipid profile and lipoprotein content to atherogenicity.     

The intensity of processes of lipoperoxidation and antioxidant defense in patients with recurrent viral herpes infection

The article discusses some parameters of free radical metabolism of lymphocytes of blood plasma in 65 patients with recurrent virus herpes infection in course of disease. It is established that in patients occurs increasing of both of level of malonic dialdehyde and functional activity of neutrophils in blood plasma. On the background of these alterations, compensatory increase of activity of such antioxidant enzymes as ceruloplasmin and catalase is noted. The intensity of stationary derangement of free radical oxidation and antioxidant defense under recurrent virus herpes infection depended on the period of disease and severity of pathologic process.     

Lipid peroxidation and resistance to oxidation in patients with type 2 diabetes mellitus

We investigated lipid peroxidation, resistance of plasma and red blood cells to oxidation, and antioxidant defense system in erythrocytes and sera in patients with type 2 diabetes mellitus. One group included newly diagnosed 20 patients and the other included 20 patients treated with oral antidiabetic agents (OAD). Twenty healthy subjects served as controls. Serum and red blood cell malondialdehyde (MDA), glutathione (GSH), resistance to oxidation, and plasma thiol (total -SH) levels were measured. In addition, glycated hemoglobin, serum fructosamine, uric acid, total protein, total cholesterol, triglyceride and glucose levels were determined. Although newly diagnosed patients had higher serum and erythrocyte MDA levels than those of controls, the highest levels of MDA were determined in patients treated with OAD. MDA levels after exposing to oxidation increased in OAD group more than in newly diagnosed patients. Total -SH and erythrocyte GSH levels of the both diabetic groups were lower than controls. These results show that serum and erythrocyte lipid peroxidation was increased in diabetic patients. The sera of the patients showed a decreased resistance against oxidation. We therefore suggest that the effect of increased free radicals may be prevented by antioxidant systems in early stages of type 2 diabetes but in advanced stages this relationship is impaired owing to decreased antioxidant activity. Decreased red blood cell GSH and serum total -SH levels may be due to a compensation mechanism of the antioxidants.