Plasma Total Thiol Research Articles

Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients

The aim of this work was to study the association between plasma thiol levels and percentage carotid narrowing in a group of 68 patients who underwent a carotid endarterectomy, pertained as a risk factor for vascular and cardiovascular disease. Total plasma thiols were measured by capillary electrophoresis laser-induced fluorescence. The mean values of the hematological parameters studied were within normal limits and 25% of the patients were hyperhomocysteinemic (homocysteine >15 micromol/L). Pearson's correlation between carotid narrowing degree and the most common risk factors for atherosclerosis showed a positive relationship only between carotid narrowing degree and cysteine levels (r=0.252; p<0.05). Stepwise multiple linear regression with carotid narrowing degree as the dependent variable, and cysteine, homocysteine, age, triglyceride and low-density lipoprotein-cholesterol as independent variables confirmed that cysteine was significantly associated with these variables. By regrouping the population according to cysteine and homocysteine concentration percentiles, we found positive correlation between these parameters and median values of carotid narrowing degree. Our study provides experimental evidence to confirm that plasma homocysteine and cysteine are involved in carotid narrowing after carotid endarterectomy intervention, suggesting that cysteine may be involved in the deleterious molecular mechanisms active in carotid stenosis.

Comparison of protein carbonyl and total plasma thiol concentrations in patients with complete hydatidiform mole with those in healthy pregnant women

Background. Normal pregnant women are known to have increased oxidative stress and lipid peroxidation (which can be estimated by protein carbonyl concentration) but offsetting antioxidant protection (of which plasma thiols are an important component). Aim. This study set out to compare levels of these markers in normal pregnant women and patients with complete hydatidiform mole (CHM). Methods. Blood was taken from 41 healthy pregnant women and 39 patients with CHM attending a university hospital, and protein carbonyl and thiol levels determined spectrophotometrically on plasma. Statistical analysis of the results was performed using Student's t-test and Pearson's correlation. Results. Patients with CHM were found to have significantly higher levels of protein carbonyls and lower (but non-significant) levels of thiols. Conclusion. The results may indicate oxidative stress as a feature of CHM.

Early evolution of selenium status and oxidative stress parameters in rat models of thermal injury

The objective of the present study was to measure the relationship between selenium status and oxidative stress in two rat models of thermal injury. A non-lethal third-degree burn injury involving 20% (experiment 1) or 40% (experiment 2) of total body surface area (TBSA) was applied to male Wistar rats. Selenium level, glutathione peroxidase (GPx) activity in plasma, red blood cells (RBC) and tissues (liver, kidney, muscle, and brain), and plasma selenoalbumin (Se-alb) were measured in control rats and in burned rats respectively 6 hours after injury and daily from day 1 to day 5. In parallel, lipid and protein oxidative damages, monitored by plasma and tissue thiobarbituric acid reactive species (TBARs) levels and plasma total thiol groups were assessed. We observed a decrease of plasma Se and Se-albumin 6 hours after burn injury. In parallel, plasma GPx activity rapidly decreased and remained significantly lower than in control rats. These alterations were enhanced by the burn injury severity. Plasma TBARs followed the same pattern as that of plasma cholesterol, with an initial decrease and an increase at day 3 in 40% TBSA burned rats. Plasma thiol groups decreased in the two experiments indicating plasma protein oxidation. These results confirm an early oxidative stress in burn injury, and suggest an early selenium mobilization, which might counteract this oxidative stress. These data underline the crucial need of a restored selenium status in burned patients immediately after the burn injury.

N-methyl-D-glucamine improves the laser-induced fluorescence capillary electrophoresis performance in the total plasma thiols measurement.

We describe an ultrarapid capillary electrophoresis with laser-induced fluorescence (CE-LIF) method for total plasma thiols measurement. Reduced thiols by 10% tri-n-butylphosphine (TBP) were derivatized in 10 min at room temperature with 5-iodoacetamidofluorescein (5-IAF) as fluorescent reagent. We show that CE-LIF allows a baseline separation of total plasma cysteinylglycine, homocysteine, cysteine, and glutathione in less than 5 min when N-methyl-D-glucamine in run buffer was added. CE was compared with high-performance liquid chromatography (HPLC) with fluorescence detection. The Bland-Altman test and Passing-Bablok regression demonstrates that the results obtained by CE-LIF and by HPLC are highly comparable. The simplified procedure of sample preparation, the short incubation and fast separation times, the high specificity, sensitivity and reproducibility, and the lower cost of analysis suggest that our proposed method can be considered valuable for the automation analysis in a routine laboratory.

Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease

Objectives: As an important risk factor for coronary atherosclerosis, elevated plasma total homocysteine (t-hcy) concentration has recently received greater attention than have conventional risk factors. Though less reactive than homocysteine, cysteine (cys) is the most abundant plasma thiol and may function as an extracellular regulating factor of thiol/disulfide exchange in order to maintain an adequate redox status. An increase in the total amount of this compound may be noxious depending on environmental conditions. In the present study, the aim was to investigate changes of plasma total cysteine, homocysteine and other determinants in different types of coronary heart disease. Design and methods: Plasma total homocysteine (t-hcy), cysteine (t-cys), cysteinylglycine (t-cysgly), folic acid, vitamin B 12, lipid parameters, total protein, albumin and creatinine levels were studied in plasma from 68 patients with coronary heart disease and 42 healthy controls. After reduction of disulfide bonds with tri- n-buthylphosphine, plasma total thiols were assayed using high performance liquid chromatography (HPLC) and fluorescence detection following derivatization of sulfhydryl groups with 7-fluoro-benzo-2-oxa-1,3-diazole-4-sulfonate (SBD-F). Other parameters were determined by using commercial kits. Results: Plasma t-hcy and t-cys levels were higher in patients ( P<0.0001) than in controls, but t-cysgly was unchanged. Hcy and cys levels were correlated with age in the whole study population ( r=0.49, r=0.46, P<0.01). Plasma t-hcy positively correlated with plasma t-cys ( r=0.53, P<0.01) and t-cysgly ( r=0.49, P<0.01) in patients, and with plasma t-cys ( r=0.57, P<0.01) in controls. Postmenopausal women had higher t-cys and t-hcy levels than premenopausal women among the controls ( P<0.01). Folate and vitamin B 12 levels were similar in both patients and controls. Patients with vitamin B 12 levels below normal had higher plasma t-cys and t-cysgly levels ( P<0.05). Interestingly, control subjects with lower vitamin B 12 levels had lower plasma t-hcy levels ( P<0.05). Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, total protein, albumin and creatinine levels in patients and controls were within the normal range, but only HDL-cholesterol levels in patients were lower than in controls ( P<0.0001). Triglyceride and VLDL levels of patients were also higher than those of controls ( P<0.0001). Conclusions: Higher plasma total cysteine levels are as important as higher plasma total homocysteine levels. Both parameters are intercorrelated and may act synergistically. To discern their respective roles in atherosclerotic disease, these aminothiol levels have to be considered together.

Plasma total antioxidant capacity in hemodialyzed patients and its relationships to other biomarkers of oxidative stress and lipid peroxidation.

Patients undergoing long-term hemodialysis (HD) exhibit increased levels of oxidative stress, likely contributing to the increased rate of cardiovascular disease. The present study represents a critical evaluation of some of the most widely used oxidative indicators, as applied to the monitoring of hemodialysis-associated oxidative stress. Total plasma antioxidant capacity was determined by two independent procedures, the total antioxidant status (TAS) and the ferric reducing ability of plasma (FRAP) methods. Plasma lipid peroxidation was assessed by determining the peroxidation products malonaldehyde and 4-hydroxynonenal (MDA-4HNE) as well as lipid hydroperoxides ("Fox-2" and "d-ROMs" methods). Total plasma thiols and plasma alpha-tocopherol were also determined. MDA-4HNE levels were higher in HD patients and decreased following HD, possibly due to passive diffusion across dialysis filters. d-ROMs were also higher in HD patients but exhibited a further increase following the dialysis procedure. Serum alpha-tocopherol did not show any significant differences. Plasma thiols were lower in HD patients and were restored following HD. Plasma total antioxidant capacity determined with either method was unexpectedly higher in HD patients compared to controls, and decreased following HD. These data indicate that, of the biomarkers studied, d-ROMs level is the one more accurately reflecting the oxidative alterations taking place in HD patients, while determination of MDA-4HNE fails to detect oxidation occurring during the HD sessions. In addition, our findings point out that the determination of total antioxidant capacity in HD patients is severely affected by the concomitant fluctuations in plasma urate levels and therefore needs careful interpretation.

Effects of aminoguanidine and desferrioxamine on some vascular and biochemical changes associated with streptozotocin-induced hyperglycaemia in rats

The effects of aminoguanidine (AG; 100 mgkg−1) and desferrioxamine (DFO; 50 mgkg−1) on some vascular and biochemical changes associated with streptozotocin (STZ; 65 mgkg−1; i.p.)-induced hyperglycaemia were investigated in rats. Both AG and DFO were administered i.p., once daily, for 14 consecutive days to normal and hyperglycaemic animals. The responsiveness of the isolated aortic rings to phenylephrine (PE) was tested. In addition, biochemical markers for oxidative stress such as plasma levels of lipid peroxides and total thiols, as well as the activities of erythrocytic superoxide dismutase (SOD) and whole blood glutathione peroxidase (GSH-Px) were assessed. Results of the present study indicated that induction of hyperglycaemia was associated with increased aortic ring responsiveness to PE, loss in body weight, increase in urine volume, elevation of plasma total thiols and lipid peroxide levels and elevated SOD and GSH-Px enzymatic activities. Treatment of normal rats with AG reduced the response of their aortae to PE. Furthermore, a profound increase in body weight without any significant change in the measured biochemical parameters was observed. In hyperglycaemic animals, AG tended to normalize the enhanced aortic response to PE and modulated STZ-induced biochemical changes without affecting the elevated plasma glucose level. Treatment of normal rats with DFO reduced the response of their aortae to PE and decreased their body weight without altering any of the chosen biochemical parameters. In hyperglycaemic animals, DFO attenuated the responsiveness of their aortae to PE and at the same time, did not affect the loss in body weight and the elevation of plasma glucose level observed in the hyperglycaemic group. Additionally, DFO normalized the elevated plasma level of total thiols and exerted a modulatory influence on the enhanced activities of SOD and GSH-Px as well as on the increased levels of lipid peroxides. Our data lend further credence for the contribution of oxidative stress in the vascular and biochemical changes associated with STZ-induced hyperglycaemia. It is also apparent that advanced glycosylation end products and nitric oxide might be involved. Until clinical studies prove the efficacy and safety of these drugs, specific agents which could scavenge free radicals and block protein glycosylation seem beneficial as a helpful adjunct to the therapy of diabetes.

Possible oxidative stress involvement in congenital dyserythropoietic anemia type 1.

Congenital dyserythropoietic anemia type 1 (CDA1) patients may suffer from iron overload, associated with oxidative damage. The aim of this study was to evaluate possible involvement of oxidative stress in the pathogenesis of CDA1. : Blood samples from 10 children diagnosed as CDA1 patients from five Bedouin families, were studied. In this study, activities of superoxide dismutase and catalase were evaluated as well as methemoglobin, plasma total thiols, plasma total antioxidant capacity and glycerol lysis time. Normal values were found for superoxide dismutase, methemoglobin, trolox equivalent antioxidant capacity and total plasma thiols in CDA1 patients. However average catalase levels were significantly reduced (P<0.001) and glycerol lysis test was significantly prolonged (P<0.001). Ferritin levels, which were slightly increased in all patients, positively correlated with catalase values (r = 0.74, P = 0.022). Oxidative stress has not been proven in CDA1 pediatric patients. Some indications of oxidative damage exist, but it may not be directly related to the mechanism of anemia.

OXIDANT AND ANTIOXIDANT SYSTEMS IN NIDDM PATIENTS: INFLUENCE OF VITAMIN E SUPPLEMENTATION

Free radical-mediated oxidative stress has been implicated in adverse tissue changes in a number of diseases. In view of the role of oxidative processes in non-insulin dependent diabetes mellitus (NIDDM), in this study, we investigated the oxidant and antioxidant status of plasma in patients with NIDDM and the effect of vitamin E (800 IU/day) supplementation on oxidative stress, antioxidant defense system, fructosamine levels and insulin action. Thirty controls and 40 NIDDM patients were studied. In controls and patients, plasma lipids, vitamin E, lipid peroxide, total thiols (t-SH), superoxide peroxidase (SOD) and glutathione peroxidase (GPx) were measured in the basal state and after vitamin E (800 IU/d) supplementation for a month. All lipids and lipid fractions in plasma were significantly decreased, whereas the HDL-C level was changed in diabetic patients supplemented with vitamin E when compared with baseline values. Vitamin E administration also significantly reduced fasting glucose and fructosamine levels, whereas increased significantly reduced fasting glucose and fructosamine levels, whereas increased significantly plasma C-peptide and insulin levels (p < 0.01, p < 0.001, respectively). Following vitamin E supplementation, TBARs levels were found to be significantly lower (p < 0.001) than the baseline value NIDDM patients are. On the other hand, activities of GPx and SOD were significantly higher (p < 0.001) than baseline values. A similar trend was observed for total thiols contents, but in this case, the increase was not significant. In conclusion, this study demonstrates that vitamin E improved beta-cell function and increased plasma insulin and C-peptide levels, possibly by inducing the antioxidant capacity of the organism and/or reducing the peripheral resistance in NIDDM. Long-term studies are needed to demonstrate the beneficial effects of vitamin E on treatment/prevention of NIDDM.

Oxidative protein damage in early stage Type 1 diabetic patients

To examine the influence of oxidative stress on oxidative protein damage, we studied 51 young Type 1 diabetic patients clinically free of complications and 48 healthy normolipidaemic age-matched controls. We determined: (1) plasma carbonyl (PCO), plasma total thiol (T-SH), and nitrotyrosine (NT) levels as markers of oxidative protein damage; (2) plasma lipid hydroperoxide (LHP), and nitric oxide (NO) levels as markers of oxidative stress; (3) plasma total antioxidant capacity (TAO), ceruloplasmin (Cp), transferrin (TRF), unsaturated iron binding capacity (UIBC), erythrocyte glutathione (GSH), and erythrocyte superoxide dismutase (SOD) as markers of free radical scavengers. There were no significant differences in the levels of these markers between prepubertal diabetic patients and the controls. The levels of both of PCO and LHP were increased in adolescent and young adult Type 1 diabetic patients with respect to their controls. In the adolescent group, patient versus control values for PCO were 1.04±0.067 versus 0.67±0.0274 nmol/mg and for LHP they were 2.10±1.09 versus 1.00±0.4 nmol/mg. In the young adult group, patient versus control values for PCO were 0.99±0.054 versus 0.66±0.02 nmol/mg and for LHP they were 1.96±0.78 versus 1.15±0.4 nmol/mg. TAO levels were significantly decreased in adolescent diabetic patients compared to their controls (0.92±0.27 vs. 1.86±0.37) and in young adult diabetic patients compared to their controls (0.80±0.27 vs. 2.11±0.54 nmol/mg). T-SH was not different between diabetic patients and the controls. Serum NT, NO, and erythrocyte SOD levels were not different either between three groups of diabetic patients or between the patients and their controls. We attribute this lack of difference to limited disease duration. Changes in markers of oxidative stress other than NT, NO, and SOD observed in adolescent and young adult early stage Type 1 diabetic patients contribute to the imbalance in the redox status of the plasma. We attribute this imbalance to metal-catalyzed protein oxidation in both groups of Type 1 diabetic patients clinically free from complications.

EFFECTS OF HORMONE REPLACEMENT THERAPY ON PLASMA NITRIC OXIDE AND TOTAL THIOL LEVELS IN POSTMENOPAUSAL WOMEN

Improvement in endothelial function may be an important mechanism by which hormone replacement therapy (HRT) protects postmenopausal women against coronary artery disease. Our aim was to assess the effects of HRT on plasma nitric oxide (NOx) (nitrate plus nitrite) and total thiols in postmenopausal women, as these parameters are associated with enhanced endothelial functions. Thirty-five healthy postmenopausal volunteers (mean age 50.5 +/- 4.7 yr) in an academic and hospital research environment were involved in the study. Blood samples were collected, one at baseline and the second after 6 mo of HRT. Plasma NOx and total thiol levels were significantly elevated in the subjects after HRT. NOx may be of importance in the protective effects of HRT. Further, the increase of plasma antioxidant thiol levels might also contribute to the beneficial effects of HRT.

Antioxidant defence in recurrent abortion

Increased free radical activity has been implicated in the pathogenesis of recurrent abortion. This investigation was conducted to determine if changes in some parameters of the antioxidant system contribute to this condition. Plasma ascorbic acid, α-tocopherol, total thiols, ceruloplasmin, uric acid, albumin, and erythrocyte glutathione (GSH) were assayed in 25 nonpregnant (NP) healthy women, 25 normotensive pregnants (NTP), and 120 women with recurrent abortion. Recurrent aborters were divided into four subgroups according to the etiology: autoimmune (AUTO, n=25), luteal phase defect (LPD, n=25), anatomical defect (AD, n=20) and unexplained (UNEx, n=50). Plasma levels of ascorbic acid, α-tocopherol, and erythrocyte GSH were significantly decreased in AUTO, UNEx and LPD subgroups than those in two control groups and the AD group (ANOVA). Plasma thiols of UNEx and AUTO aborters were diminished according to controls and other abortion subgroups (ANOVA). Ceruloplasmin levels showed a decline in AUTO and UNEx subgroups when compared to controls, AD and LPD aborters (ANOVA). When UNEx, AUTO and LPD recurrent abortion subgroups were compared with each other (Student’s t-test) total thiols and erythrocyte GSH of UNEx and AUTO subgroups were diminished in comparison with LPD. We suggest that decreased concentrations of plasma ascorbic acid, α-tocopherol, total thiols and erythrocyte GSH in UNEx, AUTO and LPD reflect the increased oxidative stress, expressing a progress of the condition. Also, the imbalance between antioxidant defence and free radical activity is more evident in the AUTO subgroup. As a conclusion, although impaired antioxidant defence may be responsible for recurrent abortions, the recurrent abortions may also result in oxidative stress and depletion and weakness of antioxidant defence.

Clastogenic Factors as Biomarkers of Oxidative Stress in Chronic Hepatitis C

Background/Aims: Clastogenic factors (CFs) are composed of lipid peroxidation products, cytokines and other oxidants with chromosome-damaging properties. They are regularly observed after radiation exposure and in chronic inflammatory diseases, where they are supposed to be risk factors for carcinogenesis. It appeared of interest to investigate their presence in the plasma of patients with chronic hepatitis C. Methods: CFs are detected by chromosomal breakage studies. They were compared to malondialdehyde (MDA), total plasma thiols (t-SH), alanine aminotransferase (ALT), viral load and histological data. Results: CFs were increased in 19 of 20 patients, 16 had increased MDA levels and 15 had decreased t-SH levels. Mean values were significantly different from the 20 controls (p < 0.001). After the first 3 months of interferon treatment, all three markers showed significant improvement, but were not completely normalized. There was a positive correlation between CFs and necroinflammatory activity (p < 0.03), while MDA was correlated with fibrosis (p < 0.03). Viral load was correlated with necrosis and inflammation (p < 0.05). Conclusion: The presence of CFs in chronic hepatitis C confirms the occurrence of oxidative stress in this disease and could be useful in clinical trials for testing antioxidants. The CF test is a sensitive assay for the detection of oxidative stress and correlates with necroinflammatory activity.

Oxidative Protein Damage in Type I Diabetic Patients With and Without Complications

To examine the influence of oxidative stress on oxidative protein damage, we studied 47 Type I diabetic patients with and without complications. We determined plasma protein carbonyl, plasma protein thiol and nitrotyrosine levels as markers of oxidative protein damage, plasma lipid hydroperoxide levels as markers of oxidative stress, and plasma total thiol, plasma nonprotein thiol, erythrocyte glutathione, plasma ceruloplasmin, transferrin and total iron binding capacity as markers of free radical scavenging. There were no significant differences in nitrotyrosine, total plasma thiol, protein thiol, and erythrocyte glutathione levels between diabetic patients with complications and without complications. However, plasma protein carbonyl, lipid hydroperoxide, and nonprotein thiol levels were significantly increased in diabetic patients with complications compared with diabetic patients without complications. Although redox status of plasma is impaired in diabetic patients, we suppose these significantly different markers reflect enhanced oxidative protein damage in diabetic patients with complications.

MODULATION OF OXIDANT STATUS BY MELOXICAM IN EXPERIMENTALLY INDUCED ARTHRITIS

Meloxicam is a new non-steroidal anti-inflammatory drug, that possesses a selective inhibition of the inducible isoform of cyclooxygenase enzyme (COX-2) relative to the constitutive one, COX-1. Oxidative stress has been documented to be involved in the aetiology of many pathological conditions. The present study aims to further explore the relationship between free radical generation and the inflammatory process, and extends more to investigate the effect of meloxicam on the oxidant status in experimentally induced arthritis, namely, Freund's adjuvant-induced arthritis in rats. Results of the present investigation revealed that animals inoculated with Freund's complete adjuvant showed a biphasic response regarding changes in the right hind paw oedema volume. During the chronic phase of the disease, arthritic animals showed an elevated plasma level of lipid peroxides, enhanced blood glutathione peroxidase activity, with depletion of plasma total thiols and albumin; while no significant effects have been observed on erythrocytic superoxide dismutase activity and plasma total proteins content, as compared to normal untreated rats. Long-term administration of meloxicam, at two dose levels, produced significant antioedemetous effect and succeeded in modulating the altered parameters affected during arthritis. The selected dose regimens of meloxicam did not show any apparent lesions in the gastric mucosa. The results of the present investigation lend further support to the reported observations concerning selective COX-2 inhibitors. The modulatory influence of meloxicam on the oxidant status, particularly on lipid peroxidation and thiols might be a relevant effect accounting for its anti-inflammatory properties.

Phospholipid hydroperoxide cysteine peroxidase activity of human serum albumin

Human serum albumin (HSA) reduced the phospholipid hydroperoxide, 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl)-l-3-phosphatidylcholine (PLPC-OOH) to the corresponding hydroxy-derivative with a high apparent affinity (Km=9. 23+/-0.95 microM). Removal of bound lipid during purification increased this activity. At physiological concentration, HSA reduced the phospholipid hydroperoxide in the absence of a cofactor. However, in the presence of a cofactor (reductant), the rate of the reaction was increased. All of the major aminothiols in plasma could act as reductants, the best being the most abundant, cysteine (Km=600+/-80 microM). For every nanomole of PLPC-OOH reduced by HSA, 1.26 nmol of cystine was formed, indicating a reaction stoichiometry of 1 mol PLPC-OOH to 2 mol cysteine. We used chemical modification to determine which amino acid residues on HSA were responsible for the activity. Oxidation of thiol group(s) by N-ethylmaleimide led to a reduction in the rate of activity, whereas reduction of thiols by either dithiothreitol or the angiotensin-converting enzyme inhibitor, captopril, increased the activity. Both N-ethylmaleimide-modified HSA and dithiothreitol-treated HSA exhibited increased apparent affinities for PLPC-OOH. For a range of preparations of albumin with different modifications, the activity on PLPC-OOH was dependent on the amount of free thiol groups on the albumin (correlation coefficient=0.91). Patients with lowered albumin concentrations after septic shock showed lowered total plasma thiol concentrations and decreased phospholipid hydroperoxide cysteine peroxidase (PHCPx) activities. These results therefore show for the first time that HSA exhibits PHCPx activity, and that the majority of the activity depends on the presence of reduced thiol group(s) on the albumin.

Low Plasma Ascorbic Acid Independently Predicts the Presence of an Unstable Coronary Syndrome

Objectives. This study sought to investigate the relations between plasma antioxidant status, extent of atherosclerosis and activity of coronary artery disease.Background. Previous studies indicate that increased antioxidant intake is associated with decreased coronary disease risk, but the underlying mechanisms remain controversial.Methods. Plasma samples were obtained from 149 patients undergoing cardiac catheterization (65 with stable angina, 84 with unstable angina or a myocardial infarction within 2 weeks). Twelve plasma antioxidant/oxidant markers were measured and correlated with the extent of atherosclerosis and the presence of an unstable coronary syndrome.Results. By multiple linear regression analysis, age (p < 0.001), diabetes mellitus (p < 0.001), male gender (p < 0.001) and hypercholesterolemia (p = 0.02) were independent predictors of the extent of atherosclerosis. No antioxidant/oxidant marker correlated with the extent of atherosclerosis. However, lower plasma ascorbic acid concentration predicted the presence of an unstable coronary syndrome by multiple logistic regression (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.40 to 0.89, p = 0.01). The severity of atherosclerosis also predicted the presence of an unstable coronary syndrome (OR 1.7, 95% CI 1.14 to 2.47, p = 0.008) when all patients were considered. When only patients with significant coronary disease were considered (at least one stenosis >50%), ascorbic acid concentration (OR 0.56, 95% CI 0.37 to 0.85, p = 0.008) and total plasma thiols (OR 0.52, 95% CI 0.34 to 0.80, p = 0.004) predicted the presence of an unstable coronary syndrome, whereas the extent of atherosclerosis did not.Conclusions. These data are consistent with the hypothesis that the beneficial effects of antioxidants in coronary artery disease may result, in part, by an influence on lesion activity rather than a reduction in the overall extent of fixed disease.

Oxidative damage to plasma proteins in adult respiratory distress syndrome.

There is evidence that patients with adult respiratory distress syndrome are under severe oxidative stress that leads to molecular damage. Oxidative stress appears to be inherent in the disease process as well as an unfortunate complication of essential treatment with oxygen. Eight critically ill patients with an established diagnosis of adult respiratory distress syndrome requiring high inspired oxygen concentrations administered by ultra high frequency jet ventilation, were studied. Three patients survived (38%). For the group as a whole, there was evidence of increased protein damage, measured on serial plasma samples as an increase in protein carbonyls (mean +/- SEM, 1.41 +/- 0.09 nmol/mg protein), compared with Intensive Care Unit (ICU) controls (1.24 +/- 0.09 nmol/mg protein), and normal healthy controls (0.940 +/- 0.04 nmol/mg protein). Protein thiol groups were decreased in the ARDS group (4.56 +/- 0.50 nmol/mg protein) compared with ICU controls (5.5 +/- 0.27 nmol/mg protein), and the normal healthy controls (6.55 +/- 0.52 nmol/mg protein). However, when ARDS patients were grouped as survivors and non-survivors, total plasma protein levels were lower in survivors (53.9 +/- 2.15 mg/ml) compared with non-survivors (78.2 +/- 4.68 mg/ml); but the protein thiol content was significantly higher (p = < 0.001) in survivors (6.24 +/- 0.09 nmol/mg protein) compared with non-survivors (3.56 +/- 0.16 nmol/mg protein). Serial plasma measurements of protein damage indicated two different patterns. Survivors had higher total plasma thiol values (protein corrected), which increased as the lung injury resolved, and failing protein carbonyl values. By contrast, non-survivors had low and failing protein thiols often accompanying rising carbonyls.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostacyclin, thromboxane and antioxidant levels in pregnancy-induced hypertension

1. Plasma 6-keto-prostaglandin F 1α (6-keto-PGF 1α, a major metabolite of prostacyclin), plasma thromboxane B 2 (TXB 2, a major metabolite of thromboxan A 2) and five antioxidants (indirect markers of reactive oxygen species) namely, plasma thiol, erythrocyte lysate thiol, erythrocyte superoxide dismutase, plasma total gluthathione and erythrocyte membrane thiol, were measured in 25 healthy non-pregnant women, 36 normotensive pregnant women and 35 women with pregnancy-induced hypertension (PIH). 2. The levels of TXB 2 were significantly increased in normal pregnant women and PIH women with or without proteinuria compared with non-pregnant women. The concentrations of TXB 2 in PIH women with proteinuria were higher than those without proteinuria ( P < 0.05). 3. The levels of 6-keto-PGF 1α in healthy non-pregnant women and PIH women with or without proteinuria were significantly lower than that in normotensive pregnant women (all of three P < 0.01). There were no significant differences between healthy non-pregnant women and PIH women with and without proteinuria. 4. The ratio of TXB 2 to 6-keto-PGF 1α was markedly elevated in PIH women with or without proteinuria compared with normotensive pregnant women and healthy non-pregnant women. The difference between PIH women with proteinuria and those without proteinuria was not significant ( P > 0.05). 5. The levels of plasma thiol, superoxide dismutase and glutathione were significantly decreased in PIH women compared with normotensive pregnant women. 6. There were significant positive correlations between the levels of prostaglandins and antioxidant activity. 7. These results demonstrate that there is an imbalance between TXB 2 and 6-keto-PGF 1α in women with PIH and decreased antioxidant levels which may reflect an increased activity of reactive oxygen species. The data suggest that the changes in the activity of reactive oxygen species may have a causative role in the abnormal pattern of TXA 2 and PGI 2 production in patients with PIH.

Free radical activity and left ventricular function after thrombolysis for acute infarction.

Experimental data suggest that reperfusion injury involving free radicals contributes to the impairment of left ventricular function after successful thrombolysis. In 72 patients presenting with acute myocardial infarction, markers of free radical activity were measured before streptokinase and two hours later. Thiobarbituric acid reactive material (TBA-RM) reflects lipid peroxidation by free radicals, and the concentration of plasma total thiols (34 patients) reflects oxidative stress. Coronary arteriography was performed at 18-72 hours after thrombolysis to determine coronary patency, and left ventricular function was assessed by ventriculography and from QRS scoring of the electrocardiogram. The infarct related artery was patent (Thrombolysis In Myocardial Infarction Trial grade 2 or better) in 60 (83%) and occluded in 12. In the 60 with a patent artery, the concentration of TBA-RM increased after streptokinase by (mean (SD)) 9.2 (14.0) nmol/g albumin, whereas in the 12 with an occluded artery TBA-RM decreased by 7.0 (11.3) nmol/g albumin (p < 0.01 between groups). In those with a patent artery the rise in TBA-RM associated with thrombolysis correlated with left ventricular ejection fraction (R = -0.41, p < 0.002), and with the QRS score (R = +0.38, p = 0.003). Plasma total thiol concentrations decreased by 12.7 (31.1) mumol/l in those with a patent artery, and this decrease associated with thrombolysis correlated with left ventricular ejection fraction (R = +0.39, p < 0.02) but not with the QRS score (R = -0.2, NS). These findings suggest that reperfusion injury mediated by free radicals may be of clinical importance in humans.