The oxidant and antioxidant systems in patients with stable stenocardia and with a history of small- and large-focus myocardial infarcts

A study was made as well as a comparison of values of the cholesterol (Chs) lipid fractions concentrations, and of those of the lipid peroxidation processes activity (LPP) and the gluthathione antioxidant system (AOS) status in male subjects aged from 45 to 59 years, healthy individuals and patients with stable angina pectoris and myocardial infarction (micro- and macrofocal) during cicatrizing stage (health resort rehabilitation stage). In patients with various forms of IHD total cholesterol is raised as are atherogenic lipoproteins, and atherogenicity index, intensification being noted of LPO along with a considerable decrease in functional potencies of AOS. Similar pattern of changes of LPO and AOS in patients with stable angina pectoris and myocardial infarction (MI) during cicatrization stage certainly warrants correction of these systems not only in acute phase of MI but at the stage of rehabilitation as well.     

Study of antiinfectious potential of recombinant tumor necrosis factor-alpha

46 patients with coronary heart disease with hypercholesterolemia were exposed to therapeutic plasmapheresis (TP) in combination with alpha-tocopherol treatment (AT). The results of 3-month follow-up with assessment of the clinical status, lipid spectrum, lipid peroxidation, concentration of ceruloplasmin indicated high hypolipidemic effectiveness of TP 2-3 weeks after the treatment as shown by inhibition of lipid peroxidation and antioxidant system. The addition of AT prolonged the hypolipidemic effect of TP, promoted optimization of plasma antioxidant potential (a rise in HDL, stabilization of ceruloplasmin levels).     

Serum beta-carotene and antioxidant micronutrients in children with cancer. The 'Cancer in Children and Antioxidant Micronutrients' French Study Group

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium for 418 children with newly diagnosed malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited in 1986-1989. Age- and sex-adjusted serum concentrations of retinol, beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. In similar models, the odds ratio (OR) comparing the highest with the lowest quintile was 2.06 (95% confidence interval [CI] 1.40-3.02) for retinol, 3.87 (95% CI: 2.54-5.90) for beta-carotene, 2.15 (95% CI: 1.48-3.10) for alpha-tocopherol, 1.29 (95% CI: 0.75-2.23) for selenium, and 1.94 (95% CI: 1.17-2.23) for zinc. The cancer sites that were associated with serum beta-carotene were, in general, leukaemia, lymphoma, central nervous system, bone and renal tumours. Moreover, leukaemia was associated with low mean serum levels of retinol, selenium and zinc. Subjects with lymphoma, bone and renal tumours also had lower mean retinol and alpha-tocopherol levels than controls. Brain tumour patients had low vitamin E levels. Low serum values of antioxidant vitamins were associated with childhood neoplasm occurrence. Some site-specific effect was reported. Low peripheral nutrient levels are not considered as cancer promoters but rather as an impairment of the body's defence mechanism occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes.     

Lipid peroxidation and the system of antioxidant protection in patients with chronic glomerulonephritis and normal kidney azoturic function

As indicated by blood tests, chronic glomerulonephritis (CGN) patients with intact renal function have impaired lipid peroxidation and antioxidant defense. In nephrotic syndrome these plasm changes are more pronounced, but red cells remain relatively intact. Persistent nephrotic syndrome produces a trend to shifts in red blood picture. In CGN patients free of nephrotic syndrome red cells exhibited lipid peroxidation and weak antioxidant defense. The above facts support the validity of antioxidants use in combined treatment of CGN.     

Single umbilical artery (SUA) and congenital eye abnormalities. 2 case reports

Overall thirty patients with chronic pancreatitis were studied for expediency of differentiated employment of physiotherapeutic procedures with season of the year being taken into consideration. Shown during the course of treatment was a high clinical efficiency of inhibition of the lipid peroxidation processes and activation of glutathione link of the antioxidant system of defence. Combined use of CMC and phonophoresis with solcoseril ointment and 10% methyluracil ointment makes for enhancement of general bodily resistance, promoting more prolonged remission.     

Lipid peroxidation and antioxidant system activity in patients with duodenal peptic ulcer depending on the typological traits of their nervous activity

Condition is studied of lipid peroxidation and activity of blood serum antioxidant system in patients with duodenal ulcer depending upon their typological and individual traits. It has been ascertained that psychological and neurotic abnormalities tend to aggravate the course of ulcer disease, activate free radical processes in the presence of decline in general (total) antioxidant activity of blood serum and components thereof.     

The influence of vitamin C and e or beta-carotene on peroxidative processes in persons with myocardial ischemia

An increasing body of evidence suggests that beside hypercholesterolemia peroxidative processes and natural antioxidant defence system play important role in the development of atherosclerosis. Our earlier investigation showed the increased intensity of the peroxidative processes in the course of the acute myocardial infarction and unsatisfactory tocopherol, ascorbic acid and retinol status. The purpose of the present study was the evaluation of the effect of antioxidant vitamins supplementation by the period of 21 days on the peroxidative processes in patients after heart attack or after "bypass" admitted to the cardiological rehabilitation centre. Daily oral supplementation with vitamin C, E and beta-carotene decreased significantly plasma lipid peroxide concentration (TBARS). The highest drop in TBARS activity was found in the group after bypass. No significant effect of vitamin supplementation was observed on antioxidant enzymes activity.     

Cigarette smoke extract inhibits plasma paraoxonase activity by modification of the enzyme''s free thiols

The antioxidant effect of melatonin on LDL oxidation was studied in vitro using either a thermolabile initiator or copper ions to induce lipid peroxidation. Loading of LDL with melatonin showed only weak protection against oxidative damage as compared to alpha-tocopherol. In the presence of high concentrations of melatonin (1000 mol/mol LDL) in the medium a clear protective effect was found during lag- and propagation phase, albeit weaker than after loading with alpha-tocopherol. It is concluded that melatonin is not incorporated into LDL in sufficient concentrations to prevent lipid peroxidation effectively. When melatonin is present in the incubation medium during oxidation, a partitioning equilibrium between aqueous and lipid phase is established. Only under these conditions can melatonin act as a chain breaking antioxidant. The concentrations required, however, are far beyond those found in human plasma. Therefore, the data in this study do not support a direct physiological relevance of melatonin as an antioxidant in lipid peroxidation processes.     

U-101033E (2,4-diaminopyrrolopyrimidine), a potent inhibitor of membrane lipid peroxidation as assessed by the production of 4-hydroxynonenal, malondialdehyde, and 4-hydroxynonenal--protein adducts

4-Hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) are major lipid peroxidation products generated by free radical attack on membranes and appear to contribute to the cytotoxic effects of oxidative stress by a mechanism involving adduct formation with cellular proteins. In the present studies, we investigated the relationship between lipid peroxidation and eventual inactivation of plasma membrane proteins using a model system consisting of purified red blood cell membranes and Fe2+/EDTA. Using this system, we also analyzed the ability of a novel antioxidant, U-101033E (2,4-diaminopyrrolopyrimidine), to inhibit lipid peroxidation and associated protein damage. Our results demonstrated that significant levels of MDA and 4-HNE are generated in this model system, and that both aldehydes are capable of cross-linking membrane proteins. In addition, we used a monoclonal antibody to demonstrate the presence of 4-HNE-protein adducts in this system. The generation of 4-HNE-protein adducts closely paralleled the time course of lipid peroxidation and membrane protein cross-linking, suggesting that 4-HNE may contribute to membrane protein cross-linking. Analysis of U-101033E in this system showed that this antioxidant inhibited lipid peroxidation, prevented the appearance of 4-HNE-protein adducts, and strongly reduced membrane protein cross-linking, with an EC50 of 0.5 microM. We also show that these antioxidant effects were not due to the scavenging of superoxide anion. Thus, these studies demonstrate the potential usefulness of U-101033E for treating certain disease processes where lipid peroxidation plays a role in disease pathogenesis.     

Effect of lipid peroxidation on cryopreserved semen quality in patients with testicular or nontesticular cancer

OBJECTIVES: Although pre-freeze and post-thaw semen quality in patients with cancer is poor, it is not clear whether lipid peroxidation affects semen quality. This study assessed (1) whether poor semen quality in patients with cancer is caused by lipid peroxidation, and (2) whether patient age or sperm motility is associated with lipid peroxidation. METHODS: Lipid peroxidation was measured by determining malonaldehyde levels using the thiobarbituric acid method. Malonaldehyde levels were measured in cryopreserved semen specimens from patients with testicular (n = 15) or nontesticular cancer (n = 16) and normal men (control subjects, n = 20). A computer-assisted semen analyzer was used to determine the sperm concentration and motility before and after cryopreservation. RESULTS: Malonaldehyde levels did not differ in frozen-thawed semen specimens among patients with testicular (25.90 +/- 1.00 nM/10(8) sperm/hr) or nontesticular cancer (24.48 +/- 1.66 nM/10(8) sperm/hr), and control subjects (24.86 +/- 1.43 nM/10(8) sperm/hr). Malonaldehyde levels did not correlate with post-thaw sperm motility or patient age in patients with testicular or nontesticular cancer. Post-thaw sperm motility from patients with testicular or nontesticular cancer was significantly lower than that in normal subjects. CONCLUSIONS: The poor post-thaw semen quality in patients with testicular or nontesticular cancer is not related to lipid peroxidation but may be caused by other factors such as sperm membrane stress induced during the freeze-thaw process.     

The pathogenetic basis for detoxifying and antioxidant therapy in the combined treatment of chronic diffuse liver diseases

As many as 98 patients with chronic diffusive liver diseases were studied for markers of endogenous intoxication syndrome as they were for intensity of lipid peroxidation (LPO) processes, condition of the antiradical defence systems, and detoxicating effectiveness of the drug "Thiotriasoline". Revealed in the patients were intensification of LPO processes, enhancement of the glutathionic system enzymes activity, decrease in superoxide dismutase. Accumulation in blood of malonic dialdehyde and molecular LPO products is believed to be a factor of the endogenous intoxication syndrome progression. A correlation was found between activity of LPO processes, intensification of endotoxicosis and degree of activity of the inflammatory process in the liver. The results obtained attest to the need for the antioxidant and adequate detoxicative therapy. High detoxicating efficacy of the drug "Thiotriasoline" has been shown.     

Teaching on pathomorphism: past and present]

57 patients with macrofocal through-and-through myocardial infarction (MI) formed two groups. The control one (37 patients) received conventional treatment and the study one (20 patients) received adjuvant ramipril beginning from day 1 of MI and over the observation period. The patients were examined on day 1, 3, 10 and 20 from the moment of admission. MI patients of all the studied groups exhibited high level of lipid peroxidation (LP) products in the serum. Ramipril treatment produced marked correcting influence on conjugated dienes, malonic dialdehyde and degree of lipid oxidation. In MI patients on ramipril conjugated dienes level was the lowest on MI day 1-3, and malonic dialdehyde on MI day 10-20. Ramipril treatment limited alpha-tocopherol and ceruloplasmin increase in the serum. It is shown that in the mechanism of a positive effect of angiotensin-converting enzyme inhibitors in MI not only their direct pharmacological action can be involved but also a correction of LP processes and antioxidant system disturbances.     

The protective effect of metallothionein against lipid peroxidation caused by retinoic acid in human breast cancer cells

The treatment of breast cancer by retinoic acid (RA) may be mediated by lipid peroxidation. Expression of metallothionein (MT) in cancer cells, however, can protect against lipid peroxidation by scavenging hydroxyl radicals. In this study, a two-by-six factorial design was used to investigate the interactive effects of all-trans-RA and zinc (Zn)-induced MT on the growth of two human breast cancer cell lines differing in basal expression of MT and estrogen receptors; MCF7 cells express estrogen receptor, BT-20 cells do not. Cells were treated with Zn to induce MT and then treated with six RA concentrations. Cell proliferation, lipid peroxidation, MT protein, MT mRNA and glutathione concentrations were measured. BT-20 cells expressed higher constitutive MT concentrations than MCF7 cells. MT was significantly increased by Zn treatment in BT-20 cells but not in MCF7 cells. Low RA concentrations stimulated growth proliferation but higher concentrations inhibited cell proliferation. Elevated RA concentrations increased lipid peroxidation as measured by thiobarbituric acid reactive substances. There was a significant negative correlation between lipid peroxidation and cell proliferation. Growth inhibition and lipid peroxidation were reduced by Zn pretreatment in BT-20 cells but not in MCF7 cells. RA increased MT levels in both cell lines, which suggests that RA may generate free radicals which will induce MT mRNA expression. Glutathione did not appear to be a significant factor. Therefore, induction of MT by Zn may modulate the growth inhibitory effects of RA in human breast cancer cells. One mechanism of growth inhibition may be through increased lipid peroxidation. Induction of MT by RA may be one explanation for acquired RA resistance in cancer.     

Lipid peroxidation parameters and activities of lysosomal enzymes in patients with diabetes mellitus

The processes of lipid peroxidation and activities of lysosomal enzymes were studied in 56 patients with type I and II diabetes mellitus. The rate of lipid peroxidation of red cell membranes was assessed from the activities of enzymatic (NADPH-dependent) and nonenzymatic (ascorbate-dependent) lipid peroxidation, from accumulation of acylhydroperoxides, intermolecular joints, and from spontaneous red cell hemolysis. Activities of lysosomal enzymes (cathepsins, acid DNAse, and beta-galactosidase) were measured in leukoconcentrate. The activity of enzymatic system of lipid peroxidation and acylhydroperoxide content in red cell membranes were found increased. In parallel with this, a deficiency in leukocytic lysosomes of beta-galactosidase and DNAse was revealed. The detected metabolic disturbances may be regarded as one of the pathogenetic mechanisms of development of diabetic angiopathies. A relationship was revealed between changes in lipid peroxidation parameters and activities of lysosomal enzymes, on the one hand, and diabetes mellitus type and duration, on the other.     

3',5'-cAMP phosphodiesterase inhibitors in the combined treatment of patients with rheumatoid arthritis

A study was made of clinical effectiveness and mechanism of action of the inhibitor of the specific 3',5'-cAMP phosphodiesterase papaverine in a therapeutic complex of measures designed to treat RA patients involving an immunodepressive preparation free from any cytopenic effect prospidin as a basic mediator. It has been shown that the papaverine antiarthritic action is associated with its positive effects on the unspecific component of the immune-complex inflammation, viz. processes of lipid peroxidation, activity of the antioxidant system of defence as well as on the vascular tone and microcirculation. All this improves tissue metabolism, and in this way enhances efficiency of RA basic therapy.     

Oxidative stress and antioxidative status of plasma and erythrocytes in patients with vivax malaria

OBJECTIVES: To investigate the oxidative stress and antioxidative status of plasma and erythrocytes in patients with vivax malaria and healthy persons. DESIGN AND METHODS: Activities of antioxidative enzymes, rates of pathways of hexose monophosphate shunt and purine salvage, levels of lipid peroxidation, reduced glutathione, methemoglobin and sulfhemoglobin of erythrocytes were determined. Lipid peroxidation and levels of antioxidant substances were measured. RESULTS: Antioxidants levels and antioxidative enzymes activities were lower and lipid peroxidation, purine salvage rate were higher in patients group than controls. Erythrocyte glucose-6 phosphate dehydrogenase (G-6-PD) activity was not different from that of healthy subjects. CONCLUSIONS: Oxidative mechanisms were observed to be dominant compared with antioxidative mechanisms in patients with vivax malaria. Therefore, oxidative stress may be produced and maintained by the host defense mechanisms against malarial infection.     

The evaluation of the efficacy of hemosorption and plasmapheresis in IHD complicated by chronic heart failure

Hemosorption and plasmapheresis were studied for effects on lipid peroxidation, antioxidant blood activity, platelet hemostasis, microcirculation, myocardial contractility and intracardiac hemodynamics. The results demonstrated that antioxidant blood response is a key criterion responsible for decreased efficacy of hemosorption and plasmapheresis in patients with progressive angina pectoris with chronic heart failure. The results of hemosorption and plasmapheresis in the above patients may become better if an adjuvant antioxidant therapy is used.     

Lipid peroxidation in mitochondrial inner membranes. I. An integrative kinetic model

An integrative mathematical model was developed to obtain an overall picture of lipid hydroperoxide metabolism in the mitochondrial inner membrane and surrounding matrix environment. The model explicitly considers an aqueous and a membrane phase, integrates a wide set of experimental data, and unsupported assumptions were minimized. The following biochemical processes were considered: the classic reactional scheme of lipid peroxidation; antioxidant and pro-oxidant effects of vitamin E; pro-oxidant effects of iron; action of phospholipase A2, glutathione-dependent peroxidases, glutathione reductase and superoxide dismutase; production of superoxide radicals by the mitochondrial respiratory chain; oxidative damage to proteins and DNA. Steady-state fluxes and concentrations as well as half-lives and mean displacements for the main metabolites were calculated. A picture of lipid hydroperoxide physiological metabolism in mitochondria in vivo showing the main pathways is presented. The main results are: (a) perhydroxyl radical is the main initiation agent of lipid peroxidation (with a flux of 10(-7)MS-1); (b) vitamin E efficiently inhibits lipid peroxidation keeping the amplification (kinetic chain length) of lipid peroxidation at low values (approximately equal to 10); (c) only a very minor fraction of lipid hydroperoxides escapes reduction via glutathione-dependent peroxidases; (d) oxidized glutathione is produced mainly from the reduction of hydrogen peroxide and not from the reduction of lipid hydroperoxides.     

Lipid peroxidation: a review of causes, consequences, measurement and dietary influences

In this review the process of lipid peroxidation and the atherogenicity of peroxidied lipids are discussed. Recent findings with regard to the effect of selected dietary factors on susceptibility of lipids to oxidative stress and on antioxidant defences are analysed with particular reference to their potential use in the prevention and treatment of atherogenesis and, by extension, coronary heart disease. Laboratory methods of assessing antioxidant defences, lipid peroxidation and the effects of lipid peroxidation are also reviewed and discussed with particular reference to their ability to assess in vivo oxidative stress and lipid peroxidation status. A range of oxidative stress indices are presented and their limitations discussed, but the main focus is on the most commonly used laboratory test for lipid peroxidation, the thiobarbituric acid reacting substances (TBARS) test. Finally, the influence of selected dietary factors on measured peroxidation status is discussed, with particular reference to the antioxidant vitamins C (ascorbic acid) and E (alpha tocopherol) and the type of fatty acids (mono- and poly-unsaturated) in the diet.     

A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer

BACKGROUND: Most patients with advanced ovarian cancer will relapse following platinum-based combination chemotherapy and be considered for second-line treatment. Gemcitabine, a nucleoside analogue, is active against a range of solid tumors. This phase II study investigated the activity of single-agent gemcitabine in patients with recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients with FIGO stage III (34%) or IV (64%) ovarian cancer who were previously treated with platinum-containing regimens were enrolled. Patients received 1200 mg/m2 gemcitabine on days 1, 8 and 15 of a 28-day cycle. RESULTS: Patients completed an average of 3.6 cycles. Two complete and three partial responses were seen in 36 evaluable patients, for an overall response rate of 13.9% (95% CI: 4.7%-29.5%). The median survival time was 6.7 months. Toxicities were generally mild. The most common were grade 3-4 neutropenia and grade 3 leukopenia reported in 23.7% and 10.5% of patients, respectively. One patient had grade 4 pulmonary toxicity. CONCLUSION: Single-agent gemcitabine is active and well tolerated in patients with recurrent ovarian cancer.