Antioxidant protection in collagen-vascular diseases.

Alteration of redox balance in the serum of patients with systemic lupus erythematosus (SLE) and systemic vasculitis (SV) was investigated. Excess in oxidative processes has been measured through concentration of lipid peroxides which was found to increase by 26% in SLE and 32% in SV. Antioxidant protection capacity against this oxidative aggression has been assessed both by determining the level of activity of the enzymes participating in this process (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase GSH-Px) and by determining the total antioxidant serum activity. The results have shown that, within antioxidant protection of the body against oxidative stress, glutathione peroxidase plays the most important role and its activity is significantly affected by the great concentration of lipidic peroxides. We have also shown that there is positive correlation (r = 0.91) between the level of lipidic peroxides and the extent to which the tissue is affected. The latter is assessed by studying the serum activity of lactate dehydrogenase. Therefore, these two biologic parameters are shown to be very useful when the study of the development of the diseases is undertaken.

Lipoproteins, lipidic peroxidation and total antioxidant capacity in serum of aged subjects suffering from hyperglycemia.

Quantitative alterations of serum lipoproteins were studied as well as lipidic peroxidation level and total antioxidant capacity in the serum of 265 subjects ranging in age between 60-70 years, out of which 97 showed levels of glycemia higher than normal. Increase of LDL and VLDL was found in 74.6% respectively 67% of the old-aged subjects researched, without also finding significant differences between sexes. Frequent association between the two metabolic disorders is seen without there being a statistical correlation between degree of dyslipidemia and blood glucose level. The level of lipid peroxidation, determined by serum malondialdehyde (MDA) concentration, is higher in subjects with dyslipidemia where glycemia level exceeds 200 mg%. Total antioxidant defence in old aged hyperglycemic patients decreases by 18% as against the value seen in the controls. The normally glycemic patients show a decrease in this activity by only 12%. Significant frequency of dyslipidemia in the old aged studied is associated with hyperglycemia and can be accounted for beyond biologic mechanisms characteristic of aging, through a deficient diet. Association of dyslipidemia with hyperglycemia, the high level of lipidic peroxides and the diminution of body capacity of annihilating them, actually represents an increase in risk factors for onset of vascular attacks.

Oxidant stress and antioxidant protection in lupus nephropathy.

In a group of 65 patients with lupus nephropathy the level of lipid peroxidation and of the capacity of antioxidant protection was followed up as influenced by the activity of superoxide dismutase (SOD), of catalase (CAT) and of glutathione peroxidase (GSH-Px) as well as of the concentration of glutathione. The determinations were made in total blood and the results were compared with those obtained in a control group of 30 apparently healthy subjects. The degree of lipid peroxidation seemed to be correlated with the extent of proteinuria. As compared with the normal values the activity of the three enzymes studied was decreased and did not correlate with the level of proteinuria. The decreased SOD and GSH-Px seemed to be relatively compensated by CAT activity. The level of GSH was also decreased as compared with the control values and did not correlate with the value of proteinuria. It is concluded that the great variation of individual values could be explained by the multifactorial character of the disease as well as by the metabolic response specific for every patient and by the mechanisms possibly related to the onset of renal disease.

Oxidative stress and antioxidant protection in degenerative psychoorganic syndrome in old agers.

Changes of the redox balance are reflected at the blood level in old agers--chronically intoxicated with alcohol--presenting degenerative psycho-organic syndromes (DPOS). The parameters investigated were lipid peroxidation reduced glutathione and the total SH groups. The changes of the antioxidant enzymatic system expressed by the activity of superoxide dysmutase, of glutathione peroxidase and of catalase were also followed up. It was observed that compared with the control group the lipid peroxides increased by 70.69% and the blood concentration of G-SH and of the total SH groups decreased by 46.7% and 24.76%, respectively. Likewise enzymes such as GPx and CAT presented increases of 70.4% and respectively 68.3% associated with a decrease of 23.9% of SOD activity.

Lipid peroxidase and erythrocyte redox system in systemic vasculitides treated with corticoids. Effect of vitamin E administration.

The level of plasma lipid peroxidation was followed up in 66 patients with systemic vasculitides with autoimmune pathogeny (SLE and SV) treated with corticoid compounds. The effect of vitamin E associated to this treatment was also studied. The change of the redox cycle, of the red cell glutathione, and of the glutathione peroxidase activity, an enzyme supplying antioxidant protection, were studied in parallel. The results obtained demonstrated: an increased level of lipid peroxidation in the patients treated with corticoid substances, an increase that can be explained by the dyslipidemias induced by these compounds; a decrease of the red cell G-SH concentration owing to the continuous oxidative stress in this group of diseases. This decrease was associated with a concomitant increase of oxidated glutathione. The decrease of GSH, a substrate for glutathione peroxidase, induces an inhibition of this enzyme activity. The GSH/GSSH ratio may represent a useful marker of the evolution of disease. Administration of vitamin E in association with corticotherapy has a relatively reduced effect due to the complex metabolic disturbances with a continuous character in the autoimmune pathogenic processes. The chronic disturbance of the oxidants-antioxidants balance in patients with systemic vasculitides seems to create favourable conditions for the early onset of a process of atherogenesis with severe vascular effects.

Lipid peroxidation in autoimmune systemic vasculitides. Effect of corticoid treatment on lipid peroxidation. Antioxidant protection with vitamin E.

The effect of treatment with prednisone on lipid peroxidation and on lipid metabolism generally and the effect of vitamin E on plasma lipid peroxidation were studied in a group of patients with autoimmune systemic vasculitides. Vitamin E total plasma antioxidant capacity was determined to ascertain the antioxidant efficiency of vitamin E. Treatment with prednisone was found to induce disturbances of the lipid metabolism at the level of total cholesterol and of triglycerides. The increased values of the LDL/HDL ratio showed an increased risk of vascular disturbance in the patients investigated. The high level of lipid peroxides associated with a reduced activity of the endogenous antioxidant system was found to be uninfluenced by treatment with prednisone. Treatment with vitamin E reduced the process of lipid peroxidation but the endogenous deficiency of the antioxidant capacity prevented it to resume its normal values. In spite of the antiinflammatory and antioxidant treatment the high level of lipid peroxides might induce a self-maintained chronic process which, in time, might lead to the aggravation of the degenerative vascular changes.

Lipid peroxidation and the activity of some antioxidant enzymes in patients with systemic vasculitides treated with corticoids.

The level of lipid peroxidation and the activity of superoxide dismutase and of catalase as antioxidant enzymes were studied in 54 patients with systemic vasculitides with autoimmune pathogeny as well as in a control group of patients of the same age and sex. The patients were distributed into a group without treatment, a group treated with prednisone and a group treated with prednisone and vitamin E. Lipid peroxidation is attenuated by the addition of vitamin E while the activity of the antioxidant enzymes studied in the same groups of patients is not significantly changed. The treatment with prednisone did not change the level of peroxides neither the activity of the antioxidant enzymes studied.

Lipid peroxidation and change of plasma lipids in acute ischemic stroke.

An estimation was made of the changes of the plasma lipid components and of the level of lipid peroxidation in acute ischemic stroke either as a transient accident (TLA) or as a cerebral vascular accident (CVA). The level of serum triglycerides was found significantly increased in the patients with CVA, in correlation with a decrease of the total HDL values due to the decrease of the HDL subfraction. As compared with the control group the LDL/HDL ratio presented increased values due to the decrease of the serum HDL concentration (respectively of the HDL2). The lipid peroxidation presented a more marked increase in patients with transient ischemic accident.

Circulating immune complexes and low density lipoproteins--a molecular complex or the summation of the atherogenic risk of two separate entities?

The correlation between the circulating immune complexes (CIC) and dyslipidemia was studied in a group of 150 patients with acute ischemic stroke and 50 normal controls. The object of the study was also to find out whether these two components represent a macromolecular complex with increased atherogenic capacity or only two risk factors acting separately but achieving a summation of their atherogenic power. It can be considered that in acute ischemic stroke the presence of the two risk factors constitutes a condition of acceleration of the atherogenic process, i.e., the appearance of the vascular accident. The decrease of HDL-cholesterol detected in all the subgroups studied is probably due to the decrease of the cholesterol "reverse transport" process which favours the atherogenic process. It was found that CIC and low density lipoproteins (LDL) are risk factors which act separately determining by the effects they generate a summation of their atherogenic capacity. Cholesterol and triglycerides apparently contained in the CIC structure, can be considered as a methodologic artefact due to the use of a common reagent (PEG-6000).

Effect of calcium blocking agents of the verapamil series on the myocardium mitochondrial activity in experimentally induced arterial hypertension.

Some mitochondrial biochemical parameters were determined in Wistar rats with experimentally induced arterial hypertension (AHT) treated with calcium blocking agents of the Verapamil series. The results obtained showed that succinic dehydrogenase (SDH) activity increased, in the group with AHT, by 23.4% as compared with the control group while in the group with AHT treated with Verapamil the activity of this enzyme increased by 46.7%. The NAD+ dehydrogenase activity showed a moderate increase (15.7%) in the group with AHT and an increase by 22.3% after administration of Verapamil. The mitochondrial content in thiolic groups presented an increase of 12.5% in the group with AHT and of 24.4% in the treated group. The kinetics of the mitochondrial swelling-contraction also presented changes in as much as the cycle period, first increased then partially returned to normal values after Verapamil treatment. The strongly stimulating effect of Verapamil on the enzymatic activity in the Krebs cycle was also demonstrated.

Circulating immune complexes and the complements system in lupus nephropathy.

From a group of 75 patients with systemic lupus erythematosus (SLE), 30 patients with lupus nephropathy presenting concomitant changes of the CIC level, of the complement system (C3 and C1q factors) and proteinuria were chosen for the study. In these 30 patients, no statistically significant correlation was observed between CIC level and the value of serum complement. Low serum complement was observed in 89% of the cases while low complement values associated with increases of the CIC level were observed only in 57.8% of the cases. From the values of the C3 and C1 complement factors it results that in 76.6% of the cases of lupus nephropathy the activation of complement was achieved in the classical way. The value of proteinuria presented no significant correlation with any of the parameters investigated. The serum immunogram presented varied aspects and the components of the CIC structure revealed a great diversity of this structure.

Circulating immune complexes in collagen diseases.

In a group of 75 patients with collagen diseases a study was carried out for the structural characterization of the circulating immune complexes (CIC) and the eventual detection of a correlation between these complexes and various serum biologic parameters. The results obtained have demonstrated: (a) the great variability of the structure of immune complexes even in the same type of disease and (b) the lack of correlation between the concentration of components in the CIC structure and the level of the same components in the serum. The lack of correlation may be explained by the great variety of immune complexes formation and the increase of any of the serum immunoglobulins does not necessarily mean its total or partial aggregation in the CIC structure.