Anti-oxidant status and lipid peroxidation in patients with essential hypertension

BACKGROUND: Lipid peroxidation and derived oxidized products are being intensively investigated, because of their potential to cause injury and their pathogenetic role in several clinically significant diseases. The view that an excess of lipid peroxidation products is present and relevant in the pathogenesis of human essential hypertension or in hypertension-induced damage has still not received definitive support. OBJECTIVE: To evaluate both the extent of lipoperoxidation in essential hypertensive patients and the status of enzymatic and non-enzymatic antioxidants that potentially are able to modulate it METHODS: We selected 105 newly diagnosed essential hypertensives among those referred to our hypertension outpatient clinic and compared them with 100 normotensive controls matched for age. Plasma malondialdehyde was measured by high-performance liquid chromatography after reaction with thiobarbituric acid, as an end product of lipid peroxidation; serum selenium (Se), plasma copper (Cu) and zinc (Zn), vitamins A and E, erythrocyte superoxide dismutase and glutathione peroxidase levels were evaluated as indices of oxidant balance. Differences between the groups were tested by Student's t test and chi2 test. RESULTS: Compared with controls, essential hypertension patients had higher malondialdehyde and glutathione peroxidase activities (P<0.05 for both) and Zn concentrations (P<0.001) and lower superoxide dismutase activities (P<0.005), vitamin A (P<0.05) and E (P<0.001) levels and Cu concentrations (P<0.005). We found no difference between Se levels of essential hypertensive and control subjects. CONCLUSIONS: Essential hypertension is associated with greater than normal lipoperoxidation and an imbalance in anti-oxidant status, suggesting that oxidative stress is important in the pathogenesis of essential hypertension or in arterial damage related to essential hypertension.     

Articular chondrocytes and synoviocytes in culture: influence of antioxidants on lipid peroxidation and proliferation

AIMS: Clozapine (CLZ), an atypical neuroleptic with a high risk of causing agranulocytosis, is metabolized in the liver to desmethylclozapine (DCLZ) and clozapine N-oxide (CLZ-NO). This study investigated the involvement of different CYP isoforms in the formation of these two metabolites. METHODS: Human liver microsomal incubations, chemical inhibitors, specific antibodies, and different cytochrome P450 expression systems were used. RESULTS: Km and Vmax values determined in human liver microsomes were lower for the demethylation (61 +/- 21 microM, 159 +/- 42 pmol min(-1) mg protein(-1) mean +/- s.d.; n = 4), than for the N-oxidation of CLZ (308 +/- 1.5 microM, 456 +/- 167 pmol min(-1) mg protein(-1); n = 3). Formation of DCLZ was inhibited by fluvoxamine (53 +/- 28% at 10 microM), triacetyloleandomycin (33 +/- 15% at 10 microM), and ketoconazole (51 +/- 28% at 2 microM) and by antibodies against CYP1A2 and CYP3A4. CLZ-NO formation was inhibited by triacetyloleandomycin (34 +/- 16% at 10 microM) and ketoconazole (51 +/- 13% at 2 microM), and by antibodies against CYP3A4. There was a significant correlation between CYP3A content and DCLZ formation in microsomes from 15 human livers (r=0.67; P=0.04). A high but not significant correlation coefficient was found for CYP3A content and CLZ-NO formation (r=0.59; P=0.09). Using expression systems it was shown that CYP1A2 and CYP3A4 formed DCLZ and CLZ-NO. Km and Vmax values were lower in the CYP1A2 expression system compared to CYP3A4 for both metabolic reactions. CONCLUSIONS: It is concluded that CYP1A2 and CYP3A4 are involved in the demethylation of CLZ and CYP3A4 in the N-oxidation of CLZ. Close monitoring of CLZ plasma levels is recommended in patients treated at the same time with other drugs affecting these two enzymes.     

Prevalence of hypertension and borderline hypertension in students. Comparison with a non-student group

A blood pressure detection program was conducted at the University of Zurich in June 1978. Three consecutive blood pressure measurements using random-zero mercury sphygmomanometers (n = 4) were performed in 1364 students and 440 other subjects by 8 different investigators. Height and body weight were also measured and used to calculate the body mass index (Quetelet index). Personal history, physical activity, smoking and dietary habits were analyzed with the aid of a questionnaire. In comparison to initially measured values, there was a statistically significant decrease in systolic and diastolic pressure readings as the trial proceeded (p less than 0.001). Based on the mean value of all three measurements, hypertension was observed in only 1.7% of the male and 0.9% of the female students. In the other subjects covered by the trial the comparable values were 7.9% in males and 4.5% in females. The true prevalence of hypertension (addition of those persons with normotensive blood pressure values and simultaneous antihypertensive therapy) was 1.9% in male and 1.1% in female students, whereas 12.0% of the male and 8.5% of the female non-students suffered from hypertension. The prevalence of border-line hypertension (mean value of all three tests) was 7.4% in male and 3.0% in female students. Corresponding values for the other subjects tested were 18.7% (males) and 11.6% (females).     

Enhanced plasma level of lipid peroxidation in Iranians could be improved by antioxidants supplementation

OBJECTIVE: To study the influence of supplementation with antioxidants on factors, which might increase the risk of coronary heart disease (CHD) in Iranians. DESIGN: Twenty-one male volunteers enter the prospective, single-blind, randomized study. SETTING: The supplementation was conducted at the Cardiovascular Center, University of Tehran, the biochemical analysis were carried out in the University of Graz. SUBJECTS: Twenty-one male medical students were recruited by advertisement. Five subjects were dropped out due to lack of the compliance. METHODS: One group of Iranians received 30 mg/d beta-carotene and placebo for alpha-tocopherol; the other received beta-carotene plus 400 IU alpha-tocopherol for ten weeks. Concentrations of antioxidants in plasma and low density lipoproteins (LDL), plasma lipid profile, autoantibody against oxidized LDL (oLAb) and malondialdehyde (MDA) concentrations in plasma were measured. Oxidative resistance of LDL was estimated using conjugated diene assay. RESULTS: Iranians had a significantly lower plasma levels of total cholesterol (P < 0.002), LDL-cholesterol (P < 0.01) and high density lipoprotein-cholesterol (P < 0.002), compared to healthy Austrian subjects (n = 13). Although the baseline concentrations of alpha-tocopherol and beta-carotene were comparable with Austrians, lycopene, canthaxanthin and lutein were significantly higher in Iranians (P < 0.03-0.001). In vitro oxidative resistance of LDL, measured as lag-time, was slightly higher (P < 0.01) in Iranians comparing with Austrians. Plasma MDA and oLAb concentrations were significantly higher in Iranians (P < 0.001). Both dietary supplementations reduced plasma MDA concentrations (P < 0.001-0.001). A key finding was that a supplement combined with alpha-tocopherol caused also a significant increase of oLAb concentration (P > 0.01) as well as the significant increase of lag-time (P > 0.005). CONCLUSIONS: This study shows that high plasma MDA level of Iranians can be decreased by beta-carotene supplementation with or without alpha-tocopherol. However, alpha-tocopherol is a more powerful antioxidant, which can increase the resistance of LDL to oxidation, reduce the MDA concentrations in plasma and increase autoantibodies to oLDL.     

Dynamics of lipid peroxidation and antioxidant system in patients with severe combined trauma

The objective of the study was to determine the influence of blood loss volume on lipid peroxidation (LP) process and antioxidant system (AOS) state in the patients with a heavy combined trauma. The studies were proceeded in 36 patients with a heavy combined trauma. The mean age of the patients was 40 +/- 2. A craniocerebral trauma was associated with trauma of both thorax and abdominal cavities and locomotor system. Blood loss reached 75% of circulating blood volume (CBV), mean value was 28 +/- 3%. Blood samples for the studies were obtained at admission of the patients by emergency medical service teams, and--after 4; 24 hours, 3 and 7 days after the trauma. CBV determination was made by dradioisotope method. LP and AOS state was judged from serum level of primary (conjugated dienes), secondary (malonic dialdehyde, MDA) LP products and extracellular antioxidant enzyme ceruloplasmin (CP). K coefficient, an integral indicator was used for LP-AOS system imbalance assessment. According to the obtained data, in the studied patients intensification of the LP processes manifesting in CD and MDA contents increase was most expressed from 1 to 3 days after trauma (2.0-2.6-fold, p < 0.05) and rise of TP content maximally in the 3 day 2.28-fold (p < 0.05) was observed in the there patients. At the admission of decrease (1.6-fold, p < 0.05) was registered which normalized to the 3 day. K coefficient time course study permitted to establish that as early as at the admission of the patients into the clinic its value was substantially higher than the normal one, and to the 4 hour the imbalance in the LP-AOS system increased 5.0-fold (p < 0.05). An expression of LP processes and AOS disturbances in the patients with heavy combined trauma depended on the blood loss volume. The revealed imbalance in the LP-AOS system is indicative of a necessity of inclusion antioxidants into the complex therapy.     

Comparison of cardiovascular biofeedback, neuromuscular biofeedback, and meditation in the treatment of borderline essential hypertension.

Compared the separate effects of 3 procedures for the reduction of high blood pressure (BP) in 3 treatment groups of 8 patients each (27–59 yrs old) with medically verified borderline hypertension: (a) Biofeedback for simultaneous reductions in systolic BP and heart rate was aimed directly at reductions in BP. (b) Biofeedback for reductions in integrated forearm and frontalis muscle EMG activity was aimed at general muscular relaxation. (c) Meditation relaxation based on the "relaxation response" procedure developed by H. Benson was aimed at total bodily and "mental" relaxation. Each S was studied in 2 baseline sessions, 8 training sessions, and a 6-wk follow-up. Half of the sample returned for a 1-yr follow-up. ANOVA of the 3 treatment groups over 8 training sessions, 20 trials per session, revealed significant effects for trials within sessions. However, there were no significant main effects or interactions related to differences between the treatment conditions or to changes in BP over the course of training sessions. Although all groups showed moderate reductions in BP as compared to initial values, no technique could be seen to produce a reduction in pressure greater than that observed in the baseline sessions. BPs of patients reporting for the 1-yr follow-up were not different from pretreatment baseline levels. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of alpha-1-acidic glycoprotein on neutrophil chemiluminescence and lipid peroxidation in experimental thermal trauma

Induced chemoluminescence of neutrophils was distinctly inhibited both in intact mice and the animals with thermal injury after administration of acid alpha 1-glycoprotein. At the same time, the glycoprotein decreased the rate of thermal burn-induced activation of lipid peroxidation in rat blood, skin and liver tissue. Antioxidative and therapeutic effects of acid alpha 1-glycoprotein in burns appear to be related to regulation of neutrophil activity.     

Comparison of left and right ventricular function in acute myocardial infarction

Pulmonary arterial end-diastolic and mean right atrial pressures were compared in 25 patients with acute myocardial infarction and in one patient with unstable angina. No consistent relationship was observed between these pressures. Simultaneous ventricular function curves relating the stroke work of each ventricle to its respective filling pressure were constructed on 34 occasions, dextran infusion or diuresis being used to alter the filling pressure. The curves from each ventricle were described mathematically by a quadratic (parabolic) function as well as by a straight line function and then compared by canonical correlation analysis. Alterations in the left ventricular function curves occurred with and without depression or right ventricular function curves. These hemodynamic measurements demonstrate that acute myocardial infarction can alter the relationship between left and right ventricular function.     

Inadequate control of lipid levels in patients with a previous myocardial infarction

AIM: To access the current lipid management of late survivors of acute myocardial infarction. METHODS: A systematic follow-up of all survivors who had previously been screened for enrolment into one of three randomised clinical trials in Auckland was undertaken from December 1995 to January 1997. All contacted survivors were asked to answer a questionnaire regarding their current therapy and were invited to undergo venepuncture for a lipid assay. RESULTS: Of the 1036 patients with acute myocardial infarction screened for enrolment in the three trials there were 984 (95%) who survived 30 days. At a median of 5.5 years (interquartile range 3.2-8.5) follow-up, 641 (86%) survivors agreed to have a fasting lipid test. The mean total cholesterol level was 5.7 +/- 1.1 mmol/L high density lipoprotein cholesterol 1.1 +/- 0.3 mmol/L, low density lipoprotein cholesterol 3.8 +/- 0.9 mmol/L and triglyceride level 1.9 +/- 1.1 mmol/L. Two hundred and seven (32%) patients were treated with a lipid-modifying agent. Four hundred and forty-five (69%) patients had a cholesterol level > or = 5.2 mmol/L 381 (59%) patients had a level > or = 5.5 mmol/L and 72 (11%) patients had a level > or = 7.0 mmol/L of whom 62 patients were not being treated with a lipid-modifying agent. For the 107 patients with coronary artery bypass grafts, the mean cholesterol level was 5.4 mmol/L and the mean low density lipoprotein cholesterol level was 3.7 +/- 0.9 mmol/L, with 57 (53%) patients not being treated with a "statin" or "fibrate". CONCLUSION: Lipid management is suboptimal in this high risk population of patients post-infarction and greater efforts need to be made to achieve better control. Diet is frequently inadequate in these patients at high risk and statin therapy is indicated.     

Comparison between lung and liver lipid peroxidation and mortality after zymosan peritonitis in the rat

The author presents a 3-year study of 10 cases of revisional arthroplasty utilizing the Biomet Total Toe System. The procedure is performed to eliminate pain and restore function in cases of metatarsophalangeal joint silicone elastomer implant failure. The surgeon should be familiar with the Total Toe System before attempting revision.     

Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice

OBJECTIVES: The purpose of this paper is to describe the demographic and clinical characteristics of chiropractic patients and to document chiropractic visit rates in 6 sites in the United States and Canada. METHODS: Random samples of chiropractors from 5 US sites and 1 Canadian site were selected. A record abstraction system was developed to obtain demographic and clinical data from office charts. RESULTS: Of the 185 eligible chiropractors sampled, 131 (71%) participated. Sixty-eight percent of the selected charts showed that care was sought for low back pain, while 32% recorded care for other reasons. Spinal manipulative therapy was recorded in 83% of all charts. There was a greater than 2-fold difference in the median number of visits related to low back pain per episode of care across sites. The chiropractic visit rates in the US sites and Ontario are estimated to be 101.2 and 140.9 visits per 100 person-years, respectively. CONCLUSIONS: The chiropractic use rate in these sites is twice that of estimates made 15 years ago. The great majority of patients receive care for musculoskeletal conditions of the back and neck. The number of visits per episode varies appreciably by site.     

Time-level relationship for lipid peroxidation and the protective effect of alpha-tocopherol in experimental mild and severe brain injury

OBJECTIVE: Oxygen free radical-mediated lipid peroxidation has been proposed to be one of the major mechanisms of secondary damage in traumatic brain injury. The first purpose of this study was to establish the time-level relationship for lipid peroxidation in injured brain tissue. The second purpose was to examine the protective effect of alpha-tocopherol against lipid peroxidation. METHODS: For this study, 65 guinea pigs in five groups were studied. Five of the animals were identified as a control group, and the remaining 60 animals were divided equally into four groups (Groups A, B, C, and D). Mild injury (200 g x cm) (Groups A and C) and severe injury (1000 g x cm) (Groups B and D) were produced by the method of Feeney et al. Alpha-tocopherol (100 mg/kg) was administered intraperitoneally before brain injury in Groups C and D. Five animals from each group were killed immediately after trauma, five after 1 hour, and the remaining five animals after 36 hours. Lipid peroxidation in traumatized brain tissues was assessed using the thiobarbituric acid method. RESULTS: In all groups with traumatic brain injuries, levels of malondialdehyde, a lipid peroxidation product, were higher than in the control group. The amount of lipid peroxidation was increased by the severity of the trauma. Alpha-tocopherol significantly suppressed the rise in lipid peroxide levels in traumatized brain tissues. CONCLUSION: This study demonstrates that lipid peroxidation is increased by the severity of trauma and that alpha-tocopherol has a protective effect against oxygen free radical-mediated lipid peroxidation in mild and severe brain injury.     

Involvement of lipid peroxidation in platelet signalling

A well-known signalling pathway in blood platelets consists in the release of arachidonic acid (AA) from membrane phospholipids and its specific oxygenation into bioactive derivatives. In particular, cyclic prostaglandin endoperoxides and thromboxane A2 are potent inducers of platelet functions and are produced in greater amounts when the level of lipid hydroperoxides is higher than normal, as 'physiological concentrations' of such peroxides activate the cyclooxygenation of AA. In this context, a lower activity of platelet glutathione peroxidase (GPx), the key-enzyme for the degradation of lipid hydroperoxides, has been reported in aging, which will ensure a longer life span to those peroxides. Accordingly, the biosynthesis of pro-aggregatory prostanoids is elevated in platelets from the elderly. On the other hand, fatty acids from marine origin have been recognized as inhibitors of platelet functions, and they may alter the redox status of cells. They may for instance increase the platelet GPx activity, an effect that can be prevented by antioxidants. Overall, these data point out the relevance of the redox status in platelet functions.     

Comparison of myoglobin, creatine kinase-MB, and cardiac troponin I for diagnosis of acute myocardial infarction

Serial plasma concentrations of myoglobin, creatine kinase MB (CK-MB) isoenzyme, and cardiac troponin I (cTnI) were measured in 25 patients with a confirmed diagnosis of acute myocardial infarction (AMI), and 74 patients who were suspected of AMI but were subsequently ruled out for this diagnosis. The cutoff concentration for the cTnI assay was optimally determined to be 2.5 ng/mL. Of the three markers, myoglobin had the highest clinical sensitivity (50 percent) when blood was collected between 0 to 6 h after the onset of chest pain. Assays for all serum markers used had high clinical sensitivity (> 93 percent) 6 to 24 h after onset. The CK-MB remained highly sensitive for 48 h, while cTnI was sensitive for up to 72 h. Between 72 and 150 h, cTnI had a clinical sensitivity of 70 percent as compared to 21 percent and 18 percent for myoglobin and CK-MB, respectively. The clinical specificity of cTnI for non-AMI patients was equivalent to CK-MB and significantly higher than for myoglobin. The clinical efficiency of cTnI for all samples was better than either CK-MB or myoglobin, owing mainly to the wider diagnostic window. The specificity of cTnI for 59 patients with chronic renal failure, skeletal muscle trauma and disease was better than all of these markers including cardiac troponin T (cTnT). Results of this study show that cTnI is an effective marker for the retrospective diagnosis of AMI, and consideration should be given to its use in place of CK-MB.     

Study on body mass index, lipid profile and lipid peroxidation status in coronary artery disease

Among the many known risk factors of coronary artery disease (CAD) obesity and hypercholesterolaemia are important ones. Whatever may be the risk factor, the basic pathology of CAD is deposition of altered lipids on the endothelium. One of such altered lipid is oxidatively modified low density lipoprotein (LDL). Lipid peroxidation has been assessed by several methods. Quantitation of malondialdehyde (MDA) by thiobarbituric acid (TBA) method is one of the commonly utilised method in several laboratories. In this study 40 cases of CAD were selected for evaluation. The body mass index (BMI), lipid profile and the level of lipid peroxidation (MDA) were measured. Seventeen cases (42.5%) had normal BMI (20-25), 20 cases (50%) were in the overweight range of BMI (26-30) and only 3 cases (7.5%) were in the obese group with a BMI more than 30. BMI correlated better with the level of total cholesterol (Tc), low density lipoprotein cholesterol (HDLc) and MDA. BMI did not show any correlation with triglyceride (Tg) or high density lipoprotein cholesterol (HDLc). MDA level correlated better with Tc, Tg levels and BMI, poorly correlated with LDLc and in inverse relationship was observed with HDLc.     

Prognostic significance of hypertension and albuminuria for early mortality after acute myocardial infarction

The motile enterococci with the vanC gene have intrinsic low-level resistance to vancomycin, but have not been implicated in a nosocomial outbreak. We determined the colonization rate of motile enterococci in hospitalized and nonhospitalized patients. Perianal or stool specimens were cultured in Enterococcosel broth supplemented with 6 micrograms of vancomycin per mL. Rapid motility and pigment tests were performed on all enterococci isolated. A total of 82 motile and/or pigmented enterococci were isolated from 679 patients for a colonization rate of 12.1%. There were 43 Enterococcus gallinarum, 32 Enterococcus casseliflavus, 4 Enterococcus flavescens, and 3 Enterococcus mundtii identified. The E. gallinarum vancomycin MIC90 was 32 micrograms/mL and the E. casseliflavus vancomycin MIC90 was 8 micrograms/mL.     

Ischemic tolerance and lipid peroxidation in the brain

Using a modified method of focal ischemic preconditioning (FIP) followed by permanent middle cerebral artery occlusion (MCAO), we studied the effects of ischemic tolerance on infarct volume. The FIP was achieved by obstructing the blood flow into the MCA using miniature clamps at two points simultaneously. The first point was proximal to its origin and the second was where it intersects the middle cerebral vein. In rats subjected to three short conditioning periods (3 x 3 min with 7 min reperfusion between occlusions), there were significant reductions in the infarct volume in the cerebral cortex induced by the subsequent MCAO in FIP-treated rats compared with sham-operated controls. This rapid FIP-induced ischemic tolerance to subsequent MCAO occurred within 1 day and lasted for 5 days. Tissue lipid peroxidation in the cortex was significantly reduced for up to 2 days after FIP. In contrast, lipid peroxidation increased rapidly after MCAO. A significant reduction in this increase was observed in FIP-treated rats, suggesting a correlation with the subsequent reduction in the infarct volume.     

Comparison of angiotensin converting enzyme and renin inhibition in rats following myocardial infarction

Renal and systemic hemodynamics were studied in rats 1 month after induction of myocardial infarction by ligation of the left coronary artery. The mean arterial pressure, heart rate, and cardiac index were not different from controls, but there were striking elevations in heart weight (p < 0.001), left ventricular end diastolic pressure (p < 0.002), and renal vascular resistance (p < 0.01). Renal blood flow and the percent of cardiac output perfusing the kidneys were reduced by 18% (p < 0.01) and 14% (p < 0.01), respectively. Acute angiotensin inhibition was studied at a dose of the converting enzyme inhibitor, enalapril, or the renin inhibitor, CP71362, that lowered the mean arterial pressure by 15 mm Hg in normal rats. In normal rats, enalapril and CP71362 were without effect on renal blood flow (RBF), renal vascular resistance (RR), and RBF as a percent of cardiac output. However, in rats with myocardial infarction, enalapril and CP71362 increased the RBF and RBF as a percent of cardiac output and lowered the RR to levels similar to normal controls (p < 0.02). Enalapril and CP71362 were equally effective in reducing the left ventricular end-diastolic pressure and total peripheral resistance in rats with myocardial infarction. These data demonstrate significant intrarenal vasoconstriction following myocardial infarction in the absence of detectable changes in mean arterial pressure or cardiac index. Converting enzyme inhibition or renin inhibition had similar beneficial effects on cardiorenal function, suggesting that both classes of compounds act by a similar mechanism to improve renal hemodynamics in congestive heart failure.